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Role of Interleukin-4 in Atherosclerosis  

Lee, Yong-Woo (Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University)
Hirani, Anjali A. (School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University)
Publication Information
Archives of Pharmacal Research / v.29, no.1, 2006 , pp. 1-15 More about this Journal
Abstract
Vascular endothelial cell injury or dysfunction has been implicated in the onset and' progression of cardiovascular diseases including atherosclerosis. A number of previous studies have demonstrated that the pro-oxidative and pro-inflammatory pathways within vascular endothelium play an important role in the initiation and progression of atherosclerosis, Recent evidence has provided compelling evidence to indicate that interleukin-4 (IL-4) can induce proc inflammatory environment via oxidative stress-mediated up-regulation of inflammatory mediators such as cytokine, chemokine, and adhesion molecules in vascular endothelial cells. In addition, apoptotic cell death within vascular endothelium has been hypothesized to be involved in the development of atherosclerosis. Emerging evidence has demonstrated that IL-4 can induce apoptosis of human vascular endothelial cells through the caspase-3-dependent pathway, suggesting that IL-4 can increase endothelial cell turnover by accelerated apoptosis, the event which may cause the dysfunction of the vascular endothelium. These studies will have a high probability of revealing new directions that lead to the development of clinical strategies toward the prevention and/or treatment for individuals with inflammatory vascular diseases including atherosclerosis.
Keywords
Interleukin-4; Atherosclerosis; Inflammation; Oxidative stress; Apoptotic cell death; Vascular endothelium; Molecular signaling pathways;
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1 Bowler, R. P., Sheng, H., Enghild, J. J., Pearlstein, R. D., Warner, D. S., and Crapo, J. D., A catalytic antioxidant (AEOL 10150) attenuates expression of inflammatory genes in stroke. Free Radic. Biol. Med., 33, 947-961 (2002)   DOI   ScienceOn
2 Chen, C. C. and Manning, A. M., TGF-$\beta$1, IL-10 and IL-4 differentially modulate the cytokine-induced expression of IL-6 and IL-8 in human endothelial cells. Cytokine, 8, 58-65 (1996)   DOI   ScienceOn
3 Conrad, D. J., Kühn, H., Mulkins, M., Highland, E., and Sigal, E., Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase. Proc. Natl. Acad. Sci. U.S.A., 89, 217-221 (1992)
4 Davies, M. J., Gordon, J. L., Gearing, A. J., Pigott, R., Woolf, N., Katz, D., and Kyriakopoulos, A., The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and Eselectin in human atherosclerosis. J. Pathol., 171, 223-229 (1993)   DOI   ScienceOn
5 DiCorleto, P. E. and Chisolm, G. M., Participation of the endothelium in the development of the atherosclerotic plaque. Prog. Lipid Res., 25, 365-374 (1986)   DOI   ScienceOn
6 Gimbrone, M. A., Bevilacqua, M. P., and Cybulsky, M. I., Endothelial-dependent mechanisms of leukocyte adhesion in inflammation and atherosclerosis. Ann. N. Y. Acad. Sci., 598, 77-85 (1990)   DOI
7 Gottlieb, R. A., Burleson, K. O., Kloner, R. A., Babior, B. M., and Engler, R. L., Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J. Clin. Invest., 94, 1621-1628 (1994)   DOI   ScienceOn
8 Han, J., Lee, J. D., Bibbs, L., and Ulevitch, R. J., A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science, 265, 808-811 (1994)   DOI
9 Heydeck, D., Thomas, L., Schnurr, K., Trebus, F., Thierfelder, W. E., Ihle, J. N., and Kühn, H., Interleukin-4 and -13 induce upregulation of the murine macrophage 12/15-lipoxygenase activity: Evidence for the involvement of transcription factor STAT6. Blood, 92, 2503-2510 (1998)
10 Isner, J. M., Kearney, M., Bortman, S., and Passeri, J., Apoptosis in human atherosclerosis and restenosis. Circulation, 91, 2703-2711 (1995)   DOI   ScienceOn
11 Ju, H., Behm, D.J., Nerurkar, S., Eybye, M. E., Haimbach, R. E., Olzinski, A. R., Douglas, S. A., and Willette, R. N., p38 MAPK inhibitors ameliorate target organ damage in hypertension: Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension. J. Pharmacol. Exp. Ther., 307, 932-938 (2003)   DOI   ScienceOn
12 Lee, J. C., Laydon, J. T., McDonnell, P. C., Gallagher, T. F., Kumar, S., Green, D., McNulty, D., Blemental, M. J., Keys, J. R., Landvatter, S. W., Strickler, J. E., McLaughlin, M. M., Siemens, I. R., Fisher, S. M., Livi, G. P., White, J. R., Adams, J. L., and Young, P. R., A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature, 372, 739-746 (1994)   DOI   ScienceOn
13 Lee, Y. W., Eum, S. Y., Nath, A., and Toborek, M., Estrogenmediated protection against HIV Tat protein-induced inflammatory pathways in human vascular endothelial cells. Cardiovasc. Res., 63, 139-148 (2004a)   DOI   ScienceOn
14 Lee, Y. W., Hennig, B., and Toborek, M., Redox-regulated mechanisms of IL-4-induced MCP-1 expression in human vascular endothelial cells. Am. J. Physiol. Heart. Circ. Physiol., 284, H185-H192 (2003)
15 Lee, Y. W., Hennig, B., Yao, J., and Toborek, M., Methamphetamine induces AP-1 and NF-$\kappa$B binding and transactivation in human brain endothelial cells. J. Neurosci. Res., 66, 583- 591 (2001b)   DOI   ScienceOn
16 Madhok, R., Crilly, A., Watson, J., and Capell, H. A., Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann. Rheum. Dis., 52, 232-234 (1993)   DOI
17 Lee, Y. W., Kühn, H., Hennig, B., and Toborek M., IL-4 induces apoptosis of endothelial cells through the caspase-3- dependent pathway. FBES Lett., 485, 122-126 (2000)   DOI   ScienceOn
18 Libby, P., Ridker, P. M., and Maseri, A., Inflammation and atherosclerosis. Circulation, 105, 1135-1143 (2002)   DOI   ScienceOn
19 Lukacs, N. W., Strieter, R. M., Elner, V., Evanoff, H. L., Burdick, M. D., and Kunkel, S. L., Production of chemokines, interleukin-8 and monocyte chemoattractant protein-1, during monocyte: endothelial cell interactions. Blood, 86, 2767-2773 (1995)
20 Masinovsky, B., Urdal, D., and Gallatin, W. M., IL-4 acts synergistically with IL-1 beta to promote lymphocyte adhesion to microvacular endothelium by induction of vascular cell adhesion molecule-1. J. Immunol., 145, 2886-2895 (1990)
21 Neish, A. S., Williams, A. J., Palmer, H. J., Whitley, M. Z., and Collins, T., Functional analysis of the human vascular cell adhesion molecule 1 promoter. J. Exp. Med., 176, 1583-1593 (1992)   DOI   ScienceOn
22 Saccani, S., Pantano, S., and Natoli, G., p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat. Immunol., 3, 69-75 (2002)   DOI   ScienceOn
23 Schnurr, K., Borchert, A., and Kühn, H., Inverse regulation of lipid-peroxidizing and hydroperoxyl lipid-reducing enzymes by interleukins 4 and 13. FASEB J., 13, 143-154 (1999)   DOI
24 Takeya, M., Yoshimura, T., Leonard, E. J., and Takahashi, K., Detection of monocyte chemoattractant protein-1 in human atherosclerotic lesions by an anti-monocyte chemoattractant protein-1 monoclonal antibody. Hum. Pathol., 24, 534-539 (1993)   DOI   ScienceOn
25 Simmons, P. J., Masinovsky, B., Longenecker, B. M., Berenson, R., Torok-Storb, B., and Gallatin, W. M., Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood, 80, 388- 395 (1992)
26 Simon, A. R., Rai, U., Fanburg, B. L., and Cochran, B. H., Activation of the JAK-STAT pathway by reactive oxygen species. Am. J. Physiol., 275, C1640-C1652 (1998)
27 Stanimirovic, D., Zhang, W., Howlett, C., Lemieux P., and Smith, C., Inflammatory gene transcription in human astrocytes exposed to hypoxia: roles of the nuclear factor-kB and autocrine stimulation. J. Neuroimmunol., 119, 365-376 (2001)   DOI   ScienceOn
28 Taubman, M. B., Rollins, B. J., Poon, M., Marmur, J., Green, R. S., Berk, B. C., and Nadal-Ginard, B., JE mRNA accumulates rapidly in aortic injury and in platelet-derived growth factorstimulated vascular smooth muscle cells. Circ. Res., 70, 314- 325 (1992)   DOI   ScienceOn
29 Thornhill, M. H., Kyan-Aung, A. U., and Haskard, D. O., IL-4 increases human endothelial cell adhesiveness for T cells but not for neutrophils. J. Immunol., 144, 3060-3065 (1990)
30 Verhasselt, V., Goldman, M., and Willems, F., Oxidative stress up-regulates IL-8 and TNF-$\alpha$ synthesis by human dendritic cells. Eur. J. Immunol., 28, 3886-3890 (1998)   DOI
31 Whelan, J., Selectin synthesis and inflammation. Trends Biochem. Sci., 21, 65-69 (1996)   DOI
32 Schindler, C. and Dranell Jr., J. E., Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu. Rev. Biochem., 64, 621-651 (1995)   DOI   ScienceOn
33 Wright, P. S., Cooper, J. R., Kropp, K. E., and Busch, S. J., Induction of vascular cell adhesion molecule-1 expression by IL-4 in human aortic smooth muscle cells is not associated with increased nuclear NF-$\kappa$B levels. J. Cell. Physiol., 180, 381-389 (1999)   DOI   ScienceOn
34 Wung, B. S., Cheng, J. J., Hsieh, H. J., Shyy, Y. J., and Wang, D. L., Cyclic strain-induced monocyte chemtactic protein-1 gene expression in endothelial cells involves reactive oxygen species activation of activator protein 1. Circ. Res., 81, 1-7 (1997)   DOI   ScienceOn
35 Cybulsky, M. and Gimbrone, M., Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science, 251, 788-791 (1991)   DOI
36 Kamitani, H., Geller, M., and Eling, T., Expression of 15- lipoxygenase by human colorectal carcinoma Caco-2 cells during apoptosis and cell differentiation. J. Biol. Chem., 273, 21569-21577 (1998)   DOI   ScienceOn
37 Pober, J. S., Activation and injury of endothelial cells by cytokines. Pathol. Biol., 46, 159-163 (1998)
38 Badger, A. M., Roshak, A. K., Cook, M. N., Newman-Tarr, T. M., Swift, B. A., Carlson, K., Connor, J. R., Lee, J. C., Gowen, M., Lark, M. W., and Kumar, S., Differential effects of SB 242235, a selective p38 mitogen-activated protein kinase inhibitor, on IL-1 treated bovine and human cartilage/chondrocyte cultures. Osteoarthr. Cartil., 8, 434-443 (2000)   DOI   ScienceOn
39 Baggiolini, M., Dewald, B., and Moser, B., Human chemokines: An update. Annu. Rev. Immunol., 15, 675-705 (1997)   DOI   ScienceOn
40 Boring, L., Gosling, J., Cleary, M., and Charo, I.F., Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature, 394, 894-897 (1998)   DOI   ScienceOn
41 Dunbar, C. E. and Nienhuis, A. W., Multiple myeloma. New approaches to therapy. JAMA, 269, 2412-2416 (1993)   DOI
42 Galea, P., Chartier, A., and Lebranchu, Y., Increased lymphocyte adhesion to allogeneic endothelial cells by interleukin-4 (IL- 4). Transplant. Proc., 23, 243-244 (1991)
43 Han, D. K., Haudenschild, C. C., Hong, M. K., Tinkle, B. T., Leon, M. B., and Liau, G., Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am. J. Pathol., 147, 267-277 (1995)
44 Hull, M., Lieb, K., and Fiebich, B. L., Pathways of inflammatory activation in Alzheimer's disease: potential targets for disease modifying drugs. Curr. Med. Chem., 9, 83-88 (2002)   DOI   ScienceOn
45 Ju, H., Nerurkar, S., Sauermelch, C. F., Olzinski, A. R., Mirabile, R., Zimmerman, D., Lee, J. C., Adams, J., Sisko, J., Berova, M., and Willette, R. N., Sustained activation of p38 mitogenactivated protein kinase contributes to the vascular response to injury. J. Pharmacol. Exp. Ther., 301, 15-20 (2002)   DOI   ScienceOn
46 Rollins, B. J. and Pober, J. S., Interleukin-4 induces the synthesis and secretion of MCP-1/JE by human endothelial cells. Am. J. Pathol., 138, 1315-1319 (1991)
47 Ross, R., Atherosclerosis is an inflammatory disease. Am. Heart J., 138, S419-S420 (1999)   DOI   ScienceOn
48 Zhou, Z-H. L., Chaturvedi, P., Han, Y., Aras, S., Li, Y., Kolattukudy, P. E., Ping, D., Boss, J. M., and Ransohoff, R. M., IFN-${\gamma}$ induction of the human monocyte chemoattractant protein (hMCP)-1 gene in astrocytoma cells: Functional interaction between an IFN-$\gamma$-activated site and a GC-rich element. J. Immunol., 160, 3908-3916 (1998)
49 Seger, R. and Krebs E. G., The MAPK signaling cascade. FASEB J., 9, 726-735 (1995)   DOI
50 Thornhill, M. H. and Haskard, D. O., IL-4 regulates endothelial cell activation by IL-1, tumor necrosis factor, or IFN-$\gamma$. J. Immunol., 145, 865-872 (1990)
51 Lee, Y. W., Eum, S. Y., Chen, K. C., Hennig, B., and Toborek, M., Gene expression profile in interleukin-4-stimulated human vascular endothelial cells. Mol. Med., 10, 19-27 (2004b)   DOI   ScienceOn
52 Aiello, R. J., Bourassa, P. K., Lindsey, S., Weng, W., Natoli, E., Rollins, B. J., and Milos, P. M., Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein Edeficient mice. Arterioscler. Thromb. Vasc. Biol., 19, 1518- 1525 (1999)   DOI   ScienceOn
53 Feinmark, S. J. and Cornicelli, J. A., Is there a role for 15- lipoxygenase in atherogenesis? Biochem. Pharmacol., 54, 953-959 (1997)   DOI   ScienceOn
54 Hennig, B. and Chow, C. K., Lipid peroxidation and endothelial cell injury: implication in atherosclerosis. Free Radical Biol. Med., 4, 99-106 (1988)   DOI   ScienceOn
55 Iademarco, M. F., McQuillan, J. J., and Dean, D. C., Vascular cell adhesion molecule 1: Contrasting transcriptional control mechanisms in muscle and endothelium. Proc. Natl. Acad. Sci. U.S.A., 90, 3943-3947 (1993)
56 Ikeda, U., Ikeda, M., Oohara, T., Oguchi, A., Kamitani, K., Tsuruya, Y., and Kano, S., Interleukin-6 stimulates the growth of vascular cells in a PDGF-dependent manner. Am. J. Physiol., 260, H1713-H1717 (1991)
57 Pernis, A., Witthuhn, B., Keegan, A. D., Nelms, K., Garfein, E., Ihle, J. N., Paul, W. E., Pierce, J. H., and Rothman, P., Interleukin 4 signals through two related pathways. Proc. Natl. Acad. Sci. U.S.A., 92, 7971-7975 (1995)
58 Mirnics, K., Middleton, F. A., Marquez, A., Lewis, D. A., and Levitt, P., Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron, 28, 53-67 (2000)   DOI   ScienceOn
59 Barks, J. L., McQuillan, J. J., and Iademarco, F., TNF-$\alpha$ and IL-4 synergistically increase vascular cell adhesion molecule-1 expression in cultured vascular smooth muscle cells. J. Immunol., 159, 4532-4538 (1997)
60 Grosch, S. and Kaina, B., Transcriptional activation of apurinic/ apyrimidinic endonuclease (Ape, Ref-1) by oxidative stress requires CREB. Biochem. Biophys. Res. Commun., 261, 859-863 (1999)   DOI   ScienceOn
61 Reape, T. J. and Groot, P. H., Chemokines and atherosclerosis. Atherosclerosis, 147, 213 -225 (1999)   DOI   ScienceOn
62 Kumar, S., Boehm, J., and Lee, J. C., p38 MAP kinases: Key signaling molecules as therapeutic targets for inflammatory diseases. Nat. Rev. Drug Discov., 2, 717-726 (2003)   DOI   ScienceOn
63 Watson, J. M., Berek, J. S., and Martinez-Maza, O., Growth inhibition of ovarian cancer cells induced by antisense IL-6 oligonucleotides. Gynecol. Oncol., 49, 8-15 (1993)   DOI   ScienceOn
64 Westra, J., Kuldo, J. M., van Rijswijk, M. H., Molema, G., and Limburg, P. C., Chemokine production and E-selectin expression in activated endothelial cells are inhibited by p38 MAPK (mitogen activated protein kinase) inhibitor RWJ 67657. Int. Immunopharmacol., 5, 1259-1269 (2005)   DOI   ScienceOn
65 Cesari, M., Penninx, B. W., Newman, A. B., Kritchevsky, S. B., Nicklas, B. J., Sutton-Tyrrell, K., Tracy, R. P., Rubin, S. M., Harris, T. B., and Pahor, M., Inflammatory markers and cardiovascular disease (The Health, Aging and Body Composition [Health ABC] Study). Am. J. Cardiol., 92, 522- 528 (2003)   DOI   ScienceOn
66 Fijen, J. W., Zijlstra, J. G., De Boer, P., Spanjersberg, R., Tervaert, J. W., Van Der Werf, T. S., Ligtenberg, J. J., and Tulleken, J. E., Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated proteinkinase inhibitor, in healthy human volunteers. Clin. Exp. Immunol., 124, 16-20 (2001)   DOI
67 Kishimoto, T., Interleukin-6: From basic science to medicine-40 years in immunology. Annu. Rev. Immunol., 23, 1-21 (2005)   DOI   ScienceOn
68 Ma, X. L., Kumar, S., Gao, F., Louden, C. S., Lopez, B. L., Christopher, T. A., Wang, C., Lee, J. C., Feuerstein, G. Z., and Yue, T. L., Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation, 99, 1685-1691 (1999)   DOI   ScienceOn
69 Seino, Y., Ikeda, U., Ikeda, M., Yamamoto, K., Misawa, Y., Hasegawa, T., Kano, S., and Shimada, K., Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. Cytokine, 6, 87-91 (1994)   DOI   ScienceOn
70 Seino, Y., Ikeda, U., Takahashi, M., Hojo, Y., Irokawa, M., Kasahara, T., and Shimada, K., Expression of monocyte chemoattractant protein-1 in vascular tissue. Cytokine, 7, 575-579 (1995)   DOI   ScienceOn
71 Sasaguri, T., Arima, N., Tanimoto, A., Shimajiri, S., Hamada, T., and Sasaguri, Y., A role for interleukin 4 in production of matrix metalloproteinase 1 by human aortic smooth muscle cells. Atherosclerosis, 138, 247-253 (1998)   DOI   ScienceOn
72 Kawashima, Y., Takeyoshi, I., Otani, Y., Koibuchi, Y., Yoshinari, D., Koyama, T., Kobayashi, M., Matsumoto, K., and Morishita, Y., FR167653 attenuates ischemia and reperfusion injury of the rat lung with suppressing p38 mitogen-activated protein kinase. J. Heart Lung Transplant., 20, 568-574 (2001)   DOI   ScienceOn
73 Kochx, M. M., De Meyer, G. R., Muhring, J., Bult, H., Bultinck, J., and Herman, A. G., Distribution of cell replication and apoptosis in atherosclerotic plaques of cholesterol-fed rabbits. Atherosclerosis, 120, 115-124 (1996)   DOI   ScienceOn
74 Rocken, M., Racke, M., and Shevach, E. M., IL-4-induced immune deviation as antigen-specific therapy for inflammatory autoimmune disease. Immunol. Today, 17, 225-231 (1991)   DOI   ScienceOn
75 Shyy, Y. J., Li, Y. S., and Kolattukudy, P. E., Structure of human monocyte chemotactic protein gene and its regulation by TPA. Biochem. Biophys. Res. Commun., 169, 346-351 (1990)   DOI   ScienceOn
76 Ginsberg, S. D., Hemby, S. E., Lee, V. M., Eberwine, J. H., and Trojanowski, J. Q., Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann. Neurol., 48, 77-87 (2000)   DOI   ScienceOn
77 Toborek, M. and Kaiser, S., Endothelial cell functions. Relationship to atherogenesis. Basic Res. Cardiol., 94, 295-314 (1999)   DOI
78 Adams, J. L., Badger, A. M., Kumar, S., and Lee, J. C., p38 MAP kinase: molecular target for the inhibition of pro-inflammatory cytokines. Prog. Med. Chem., 38, 1-60 (2001)   DOI
79 Gu, L., Tseng, S. C., and Rollins, B. J., Monocyte chemoattractant protein-1. Chem. Immunol., 72, 7-29 (1999)   DOI
80 Canfield, S., Lee, Y., Schroder, A., and Rothman, P., Cutting edge: IL-4 induces suppressor of cytokine signaling-3 expression in B cells by a mechanism dependent on activation of p38 MAPK. J. Immunol., 174, 2494-2498 (2005)   DOI
81 Ihle, J. N., STATs: Signal transducers and activators of transcription. Cell, 84, 331-334 (1996)   DOI   ScienceOn
82 Lavie, J., Dandre, F., Louis, H., Lamaziere, J. D., and Bonnet, J., Vascular cell adhesion molecule-1 gene expression during human smooth muscle cell differentiation is independent of NF-$\kappa$B activation. J. Biol. Chem., 274, 2308-2314 (1999)   DOI   ScienceOn
83 Neish, A. S., Khachigian, L. M., Park, A., Baichwal, V. R., and Collins, T., Sp1 is a component of the cytokine-inducible enhancer in the promoter of vascular cell adhesion molecule- 1. J. Biol. Chem., 270, 28903-28909 (1995)   DOI
84 Osborn, L., Hession, C., Tizard, R., Vassallo, C., Luhowskyj, S., Chi-Rosso, G., and Lobb, R., Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell, 59, 1203- 1211 (1989)   DOI   ScienceOn
85 Rahman, I. and MacNee, W., Regulation of redox glutathione levels and gene transcription in lung inflammation: Therapeutic approaches. Free Radic. Biol. Med., 28, 1405-1420 (2000)   DOI   ScienceOn
86 Toborek, M., Lee, Y. W., Kaiser, S., and Hennig, B., Measurement of inflammatory properties of fatty acids in human endothelial cells. Methods Enzymol., 352, 198-219 (2002b)   DOI
87 Ylä-Herttuala, S., Rosenfeld, M. E., Parthasarathy, S., Glass, C. K., Sigal, E., Witztum, J. T., and Steinberg, D., Colocalization of 15-lipoxygenase mRNA and protein with epitopes of oxidized low density lipoprotein in macrophage-rich areas of atherosclerotic lesions. Proc. Natl. Acad. Sci. U.S.A., 87, 6959-6963 (1990)
88 Polunovsky, V. A., Wendt, C. H., Ingbar, D. H., Peterson, M. S., and Bitterman, P. B., Induction of endothelial cell apoptosis by TNF alpha: modulation by inhibitors of protein synthesis. Exp. Cell Res., 214, 584-594 (1994)   DOI   ScienceOn
89 Toborek, M., Lee, Y. W., Garrido, R., Kaiser, S., and Hennig, B., Unsaturated fatty acids selectively induce an inflammatory environment in human endothelial cells. Am. J. Clin. Nutr., 75, 119-125 (2002a)   DOI
90 Luscinskas, F. W. and Gimbrone, M. A., Endothelial-dependent mechanisms in chronic inflammatory leukocyte recruitment. Annu. Rev. Med., 47, 413-421 (1996)   DOI   ScienceOn
91 Schreck, R., Albermann, K., and Baeurele, P. A., Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells. Free Radic. Res. Commun., 17, 221-237 (1992)   DOI
92 Lee, Y. W., Hennig, B., Fiala, M., Kim, K. S., and Toborek, M., Cocaine activates redox-regulated transcription factors and induces TNF-$\alpha$ expression in human brain endothelial cells. Brain Res., 920, 125-133 (2001a)   DOI   ScienceOn
93 Strieter, R. M., Wiggins, R., Phan, S. H., Wharram, B. L., Showell, H. J., Remick, D. G., Chensue, S. W., and Kunkel, S. L., Monocyte chemotactic protein gene expression by cytokine-treated human fibroblasts and endothelial cells. Biochem. Biophys. Res. Commun., 162, 694-700 (1989)   DOI   ScienceOn
94 Takeda, K. and Akira, S., STAT family of transcription factors in cytokine-mediated biological responses. Cytokine Growth Factor Rev., 11, 199-207 (2000)   DOI   ScienceOn
95 Ylä-Herttuala, S., Gene expression in atherosclerotic lesions. Hertz., 17, 270-276 (1992)
96 Brinckmann, R., Topp, M. S., Zalan, I., Heydeck, D., Ludwig, P., Kuhn, H., Berdel, W. E., and Habenicht, J. R., Regulation of 15-lipoxygenase expression in lung epithelial cells by interleukin-4. Biochem. J., 318, 305-312 (1996)   DOI
97 Geng, Y. J. and Libby, P., Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 betaconverting enzyme. Am. J. Pathol., 147, 251-266 (1995)
98 Guan, Z., Buckman, S. Y., Pentland, A. P., Templeton, D. J., and Morrison, A. R., Induction of cyclooxygenase-2 by the activated MEKK1 $\rightarrow$ SEK1/MKK4 $\rightarrow$ p38 mitogen-activated protein kinase pathway. J. Biol. Chem., 273, 12901-12908 (1998)   DOI   ScienceOn
99 Kobayashi, M., Takeyoshi, I., Yoshinari, D., Matsumoto, K., and Morishita, Y., P38 mitogen-activated protein kinase inhibition attenuates ischemia-reperfusion injury of the rat liver. Surgery, 131, 344-349 (2002)   DOI   ScienceOn
100 Ridker, P. M., Hennekens, C. H., Buring, J. E., and Rifai, N., Creactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N. Engl. J. Med., 342, 836-843 (2000a)   DOI   ScienceOn
101 Arrigo, A. P., Gene expression and the thiol redox state. Free Radic. Biol. Med., 27, 936-944 (1999)   DOI   ScienceOn
102 Craig, R., Larkin, A., Mingo, A. M., Thuerauf, D. J., Andrews, C., McDonough, P. M., and Glembotski, C. C., p38 MAPK and NF-$\kappa$B collaborate to induce interleukin-6 gene expression and release. J. Biol. Chem., 275, 23814-23824 (2000)   DOI   ScienceOn
103 Gimbrone, M. A., Topper, J. N., Nagel, T., Anderson, K. R., and Garcia-Cardena, G., Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann. N. Y. Acad. Sci., 902, 230- 239 (2000)
104 Gu, L., Okada, Y., Clinton, S. K., Gerard, C., Sukhova, G. K., Libby, P., and Rollins, B. J., Absense of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol. Cell., 2, 275-281 (1998)   DOI   ScienceOn
105 Hunt, A. E., Williams, L. M., Lali, F. V., and Foxwell, B. M., IL-4 regulation of p38 MAPK signalling is dependent on cell type. Cytokine, 18, 295-303 (2002)   DOI   ScienceOn
106 Kühn, H. and Chan, L., The role of 15-lipoxygenase in atherogenesis: pro- and antiatherogenic actions. Curr. Opin. Lipidol., 8, 111-117 (1997)   DOI   ScienceOn
107 Golub, T. R., Slonim, D. K., Tamayo, P., Huard, C., Gaasenbeek, M., Mesirov, J. P., Coller, H., Loh, M. L., Downing, J. R., Caligiuri, M. A., Bloomfield, C. D., and Lander, E.S., Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring. Science, 286, 531-537 (1999)   DOI   ScienceOn
108 Hennig, B., Toborek, M., McClain, C. J., and Diana, J. N., Nutritional implications in vascular endothelial cell metabolism. J. Am. Coll. Nutr., 15, 345-358 (1996)   DOI
109 Bouloumie, A., Marumo, T., Lafontan, M., and Busse, R., Leptin induces oxidative stress in human endothelial cells. FASEB J., 13, 1231-1238 (1999)   DOI
110 Lee, Y. W., Kühn, H., Hennig, B., Daugherty, A., and Toborek M., Interleukin-4 induces transcription of the 15-lipoxygenase-I gene in human endothelial cells. J. Lipid Res., 42, 783-791 (2001c)
111 Belkner, J., Stender, H., and Kühn, H., The rabbit 15-lipoxygenase preferentially oxygenates LDL cholesterol esters, and this reaction does not require vitamin E. J. Biol. Chem., 273, 23225-23232 (1998)   DOI   ScienceOn
112 Hall, D. J., Bates, M. E., Guar, L., Cronan, M., Korpi, N., and Bertics, P. J., The role of p38 MAPK in rhinovirus-induced monocyte chemoattractant protein-1 production by monocyticlineage cells. J. Immunol., 174, 8056-8063 (2005)   DOI
113 Hempel, S. L., Haycraft, D. L., Hoak, J. C., and Spector, A. A., Reduced prostacyclin formation after reoxygenation of anoxic endothelium. Am. J. Physiol., 259, C739-C745 (1990)
114 Hiltunen, M. O., Tuomisto, T. T., Niemi, M., Brasen, J. H., Rissanen, T. T., Toronen, P., Vajanto, I., and Yla-Herttuala, S., Changes in gene expression in atherosclerotic plaques analyzed using DNA array. Atherosclerosis, 165, 23-32 (2002)   DOI   ScienceOn
115 Blease, K., Seybold, J., Adcock, I. M., Hellewell, P. G., and Burke-Gaffney, A., Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion molecule-1 expression in human lung microvascular endothelial cells. Am. J. Respir. Cell. Mol. Biol., 18, 620-630 (1998)   DOI
116 Ylä-Herttuala, S., Lipton, B. A., Rosenfeld, M. E., Sarkioja, T., Yoshimura, T., Leonard, E. J., Witztum, J. L., and Steinberg, D., Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proc. Natl. Acad. Sci. U.S.A., 88, 5252-5256 (1991)
117 Ahmad, M., Theofanidis, P., and Medford, R. M., Role of activating protein-1 in the regulation of the vascular cell sadhesion molecule-1 gene expression by tumor necrosis factor-$\alpha$. J. Biol. Chem., 273, 4616-4621 (1998)   DOI   ScienceOn
118 Cyrus, T., Witztum, J. L., Rader, D. J., Tangirala, R., Fazio, S., Linton, M. R. F., and Funk, C. D., Disruption of the12/15-LO-IX gene diminish atherosclerosis in apolipoprotein E deficient mice. J. Clin. Invest., 103, 1597-1604 (1999)   DOI   ScienceOn
119 Schleimer, R. P., Sterbinsky, S. A., Kaiser, J., Bickel, C .A., Klunk, D. A., Tomioka, K., Newman, W., Luscinskas, F. W., Gimbrone, M. A., and McIntyre Jr., B. W., IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J. Immunol., 148, 1086-1092 (1992)
120 Badger, A. M., Griswold, D. E., Kapadia, R., Blake, S., Swift, B. A., Hoffman, S. J., Stroup, G. B., Webb, E., Rieman, D. J., Gowen, M., Boehm, J. C., Adams, J. L., and Lee, J. C., Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvantinduced arthritis. Arthritis Rheum., 43, 175-183 (2000)   DOI   ScienceOn
121 Chen, Y. W., Zhao, P., Borup, R., and Hoffman, E. P., Expression profiling in the muscular dystrophies: Identification of novel aspects of molecular pathophysiology. J. Cell Biol., 151, 1321-1336 (2000)   DOI
122 Kurzrock, R., Redman, J., Cabanillas, F., Jones, D., Rothberg, J., and Talpaz, M., Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms. Cancer Res., 53, 2118-2122 (1993)
123 Paul, W. E., Interleukin-4: a prototypic immunoregulatory lymphokine. Blood, 77, 1859-1870 (1991)
124 Pearson, G., Robinson, F., Gibson, T. B., Xu, B., Karandikar, M., Berman, K., and Cobb, M. H., Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr. Rev., 22, 153-183 (2001)   DOI   ScienceOn
125 Pohlman, T. H. and Harlan, J. M., Human endothelial cell response to lipopolysaccharide, interleukin-1, and tumor necrosis factor is regulated by protein synthesis. Cell. Immunol., 119, 41-52 (1989)   DOI   ScienceOn
126 Bochaton-Piallat, M. L., Gabbiani, F., Redard, M., Desmouliere, A., and Gabbiani, G., Apoptosis participates in cellularity regulation during rat aortic intimal thickening. Am. J. Pathol., 146, 1059-1064 (1995)
127 Sukovich, D. A., Kauser, K., Shirley, F. D., DelVecchio, V., Halks- Miller, M., and Rubanyi, G. M., Expression of interleukin-6 in atherosclerotic lesions of male apoE-knockout mice. Arterioscler. Thromb. Vasc. Biol., 18, 1498-1505 (1998)   DOI   ScienceOn
128 Tamaru, M. and Narumi, S., E-selectin gene expression is induced synergistically with the coexistence of activated classic protein kinase C and signals elicited by interleukin-1b but not tumor necrosis factor-$\alpha$ . J. Biol. Chem., 274, 3753-3763 (1999)   DOI   ScienceOn
129 Waetzig, G. H., Seegert, D., Rosenstiel, P., Nikolaus, S., and Schreiber, S., p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J. Immunol., 168, 5342-5351 (2002)   DOI
130 Bennett, M. R., Evan, G. I., and Newby, A. C., Deregulated expression of the c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-gamma, heparin, and cyclic nucleotide analogues and induces apoptosis. Circ. Res., 74, 525-536 (1994)   DOI   ScienceOn
131 Elices, M., Osborn, L., Takada, Y., Crouse, C., Luhowskyj, S., Hemler, M., and Lobb, R., VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell, 60, 577-584 (1990)   DOI   ScienceOn
132 Lee, Y. W., Son, K. W., Flora, G., Hennig, B., Nath, A., and Toborek, M., Methamphetamine activates DNA binding of specific redox-responsive transcription factors in mouse brain. J. Neurosci. Res., 70, 82-89 (2002)   DOI   ScienceOn
133 Sparrow, C. P., Parthasarathy, S., and Steinberg, D., Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J. Lipid Res., 29, 745-753 (1998)
134 Suzuki, E., Satonaka, H., Nishimatsu, H., Oba, S., Takeda, R., Omata, M., Fujita, T., Nagai, R., and Hirata, Y., Myocyte enhancer factor 2 mediates vascular inflammation via the p38-dependent pathway. Circ. Res., 95, 42-49 (2004)   DOI   ScienceOn
135 Goebeler, M., Gillitzer, R., Kilian, K., Utzel, K., Brocker, E., Rapp, U. R., and Ludwig, S., Multiple signaling pathwayss regulate NF-$\kappa$B-dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells. Blood, 97, 46-55 (2001)   DOI   ScienceOn
136 Guha, M., Bai, W., Nadler, J. L., and Natarajan, R., Molecular mechanisms of tumor necrosis factor a gene expression in monocytic cells via hyperglycemia-induced oxidant stressdependent and -independent pathway. J. Biol. Chem., 275, 17728-17739 (2000)   DOI
137 Iademarco, M. F., McQuillan, J. J., Rosen, G. D., and Dean, D. C., Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J. Biol. Chem., 267, 16323- 16329 (1992)
138 Levy, B. D., Romano, M., Chapman, H. A., Reilly, J. J., Drazen, J., and Serhan, C. N., Human alveolar macrophages have 15-lipoxygenase and generate 15(S)-hydroxy-5,8,11-cistrans- eicosatetraenoic acid and lipoxins. J. Clin. Invest., 92, 1572-1579 (1993)   DOI   ScienceOn
139 Sendobry, S. M., Cornicelli, J. A., Welch, K., Bocan, T., Tait, B., Trivedi, B. K., Colbry, N., Dyer, R. D., Feinmark, S. J., and Daugherty, A., Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties. Br. J. Pharmacol., 120, 1199-1206 (1997)   DOI   ScienceOn
140 Bennett, B. L., Cruz, R., Lacson, R. G., and Manning, A. M., Interleukin-4 suppression of tumor necrosis factor $\alpha$- stimulated E-selectin transcription is mediated by STAT6 antagonism of NF-$\kappa$B. J. Biol. Chem., 272, 10212-10219 (1997)   DOI   ScienceOn
141 Binns, R. M., Licence, S. T., Harrison, A. A., Keelan, E. T., Robinson, M. K., and Hakard, D. O., In vivo E-selectin upregulation correlates early with infiltration of PMN, later with PBL entry: MAbs block both. Am. J. Physiol., 270, H183- H193 (1996)
142 Huber, S. A., Sakkinen, P., Conze, D., Hardin, N., and Tracy, R., Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol., 19, 2364-2367 (1999)   DOI   ScienceOn
143 Lakshminarayanan, V., Drab-Weiss, E. A., and Roebuck, K. A., Hydrogen peroxide and tumor necrosis factor-alpha induce differential binding of the redox-responsive transcription factors AP-1 and NF-$\kappa$B to the interleukin-8 promoter in endothelial and epithelial cells. J. Biol. Chem., 273, 32670- 32678 (1996)   DOI   ScienceOn
144 Bjorkerud, S. and Bjorkerud, B., Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am. J. Pathol., 149, 367-380 (1996)
145 Davis, R. J., The mitogen-activated protein kinase signal transduction pathway. J. Biol. Chem., 268, 14553-14556 (1993)
146 Kishikawa, H., Shimokama, T., and Watanabe, T., Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL-6 and TNF in human aortic intima: role of cell mediated immunity in human atherogenesis. Virchows Arch. A. Pathol. Anat. Histopathol., 423, 433-442 (1993)   DOI
147 Libby, P. and Galis, Z. S., Cytokines regulate genes involved in atherogenesis. Ann. N. Y. Acad. Sci., 748, 158-168 (1995)
148 Ridker, P. M., Rifai, N., Stampfer, M. J., and Hennekens, C. H., Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation, 101, 1767-1772 (2000b)   DOI   ScienceOn
149 Rollins, B. J., Chemokines. Blood, 90, 909-928 (1997)
150 Ueda, A., Ishigatsubo, Y., Okubo, T., and Yoshimura T., Transcriptional regulation of the human monocyte chemoattractant protein-1 gene. J. Biol. Chem., 272, 31092-31099 (1997)   DOI   ScienceOn
151 Hyams, J. S., Fitzgerald, J. E., Treem, W. R., Wyzga, N., and Kreutzer, D. L., Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease. Gastroenterology, 104, 1285-1292 (1993)   DOI
152 Watson, A., Mazumder, A., Stewart, M., and Balasubramanian, S., Technology for microarray analysis of gene expression. Curr. Opin. Biotechnol., 9, 609-614 (1998)   DOI   ScienceOn
153 Chang, T. L., Peng, X., and Fu, X., Interleukin-4 mediates cell growth inhibition through activation of Stat1. J. Biol. Chem., 275, 10212-10217 (2000)   DOI   ScienceOn
154 Geiss, G. K., Bumgarner, R. E., An, M. C., Agy, M. B., van 't Wout, A. B., Hammersmark, E., Carter, V. S., Upchurch, D., Mullins, J. I., and Katze, M. G., Large-scale monitoring of host cell gene expression during HIV-1 infection using cDNA microarrays. Virology, 266, 8-16 (2000)   DOI   ScienceOn
155 McCarty, J. M., Yee, E. K., Deisher, T. A., Harlan, J. M., and Kaushansky, K., Interleukin-4 induces endothelial vascular cell adhesion molecule-1 (VCAM-1) by an NF-$\kappa$B-independent mechanism. FEBS Lett., 372, 194-198 (1995)   DOI   ScienceOn
156 Berliner, J. A., Navab, M., Fogelman, A. M., Frank, J. S., Demer, L. L., Edwards, P. A., Watson, A. D., and Lusis, A. J., Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation, 91, 2488-2496 (1995)   DOI   ScienceOn
157 Collis, A.J., Foster, M.L., Halley, F., Maslen, C., McLay, I.M., Page, K.M., Redford, E.J., Souness, J.E., and Wilsher, N.E., RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro potency. Bioorg. Med. Chem. Lett., 11, 693-696 (2001)   DOI   ScienceOn
158 Holvoet, P. and Collen, D., Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB J., 8, 1279-1284 (1994)   DOI
159 Nelken, N. A., Coughlin, S. R., Gordon, D., and Wilcox, J. N., Monocyte chemoattractant protein-1 in human atheromatous plaques. J. Clin. Invest., 88, 1121-1127 (1991)   DOI
160 Ross, R., The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature, 362, 801-809 (1993)   DOI   ScienceOn
161 Schulze, A. and Downward, J., Navigating gene expression using microarrays-a technology review. Nature Cell Biol., 3, E190-E195 (2001)   DOI
162 Lee, Y. W., Kühn, H., Hennig, B., Neish, A. S., and Toborek, M., IL-4-induced oxidative stress upregulates VCAM-1 gene expression in human endothelial cells. J. Mol. Cell. Cardiol., 33, 83-94 (2001d)   DOI   ScienceOn
163 Madamanchi, N. R., Li, S., Patterson, C., and Runge, M. S., Reactive oxygen species regulate heat-shock protein 70 via the JAK-STAT pathway. Arterioscler. Thromb. Vasc. Biol., 21, 321-326 (2001)   DOI   ScienceOn
164 Profita, M., Vignola, A. M., Sala, A., Mirabella, A., Siena, L., Pace, E., Folco, G., and Bonsignore, G., Interleukin-4 enhances 15- lipoxygenase activity and incorporation of 15(S)-HETE into cellular phospholipids in cultured pulmonary epithelial cells. Am. J. Respir. Cell. Mol. Biol., 20, 61-68 (1999)   DOI   ScienceOn
165 Behr, T. M., Nerurkar, S. S., Nelson, A. H., Coatney, R. W., Woods, T. N., Sulpizio, A., Chandra, S., Brooks, D. P., Kumar, S., Lee, J. C., Ohlstein, E. H., Angermann, C. E., Adams, J. L., Sisko, J., Sackner-Bernstein, J. D., and Willette, R. N., Hypertensive end-organ damage and premature mortality are p38 mitogen-activated protein kinase-dependent in a rat model of cardiac hypertrophy and dysfunction. Circulation, 104, 1292- 1298 (2001)   DOI   ScienceOn
166 Iwata, E., Asanuma, M., Nishibayashi, S., Kondo, Y., and Ogawa, N., Different effects of oxidative stress on activation of transcription factors in primary cultured rat neuronal and glial cells. Mol. Brain Res., 50, 213-220 (1997)   DOI   ScienceOn