Roles of ERK and NF-${\kappa}$ B in Interleukin-8 Expression in Response to Heat Shock Protein 22 in Vascular Smooth Muscle Cells

  • Kang, Seung-Hun (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Lee, Ji-Hyuk (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Choi, Kyung-Ha (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Rhim, Byung-Yong (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Kim, Koan-Hoi (Department of Pharmacology, School of Medicine, Pusan National University)
  • Published : 2008.08.31

Abstract

Heat shock proteins (HSPs) serve as molecular chaperones and play a role in cell protection from damage in response to stress stimuli. The aim of this article is to investigate whether HSP22 affects IL-8 expression in vascular smooth muscle cells (VSMCs), and which cellular factors are involved in the HSP-mediated IL-8 induction in that cell type in terms of mitogen activated protein kinase (MAPK) and transcription element. Exposure of aortic smooth muscle cells (AoSMCs) to HSP22 not only enhanced IL-8 release but also induced IL-8 transcript via promoter activation. HSP22 activated ERK and p38 MAPK in AoSMCs. HSP22-induced IL-8 release was inhibited by U0126, but not by SB202190. A mutation in the IL-8 promoter region at the binding site of NF-${\kappa}$ B, but not AP-1 or C/EBP, impaired promoter activation in response to HSP22. Delivery of I ${\kappa}$ B, but not dominant negative c-Jun, lowered HSP22-induced IL-8 release from AoSMCs. These results suggest that HS P22 induces IL-8 in VSMCs via ERK1/2, and that transcription factor NF-kB may be required for the HSP22-induced IL-8 up-regulation.

Keywords

References

  1. Aiyar N, Disa J, Ao Z, Ju H, Nerurkar S, Willette RN, Macphee CH, Johns DG, Douglas SA. Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells. Mol Cell Biochem 295: 113-120, 2007 https://doi.org/10.1007/s11010-006-9280-x
  2. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 4: 499-511, 2004 https://doi.org/10.1038/nri1391
  3. Boisvert WA, Santiago R, Curtiss LK, Terkeltaub RA. A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 101: 353-363, 1998 https://doi.org/10.1172/JCI1195
  4. Brown PH, Chen TK, Birrer MJ. Mechanism of action of a dominant-negative mutant of c-Jun. Oncogene 9: 791-799, 1994
  5. de Jong WW, Leunissen JA, Voorter CE. Evolution of the alpha-crystallin/small heat-shock protein family. Mol Biol Evol 10: 103-126, 1993
  6. Gerszten RE, Garcia-Zepeda EA, Lim YC, Yoshida M, Ding HA, Gimbrone MA, Jr., Luster A D, Luscinskas FW, Rosenzweig A. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 398: 718-723, 1999 https://doi.org/10.1038/19546
  7. Ho FM, Kang HC, Lee ST, Chao Y, Chen YC, Huang LJ, Lin WW. The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular smooth muscle cells. Biochem Pharmacol 74: 298-308, 2007 https://doi.org/10.1016/j.bcp.2007.04.008
  8. Huo Y, Weber C, Forlow SB, Sperandio M, Thatte J, Mack M, Jung S, Littman DR, Ley K. The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium. J Clin Invest 108: 1307-1314, 2001 https://doi.org/10.1172/JCI12877
  9. Inoue T, Komoda H, Nonaka M, Kameda M, Uchida T, Node K. Interleukin-8 as an independent predictor of long-term clinical outcome in patients with coronary artery disease. Int J Cardiol 124: 319-325, 2008 https://doi.org/10.1016/j.ijcard.2007.02.012
  10. Jung YD, Fan F, McConkey DJ, Jean ME, Liu W, Reinmuth N, Stoeltzing O, Ahmad SA, Parikh AA, Mukaida N. Role of P38 MAPK, AP-1, and NF-kappaB in interleukin-1beta-induced IL-8 expression in human vascular smooth muscle cells. Cytokine 18: 206-213, 2002 https://doi.org/10.1006/cyto.2002.1034
  11. Kawai T, Akira S. Toll-like receptor downstream signaling. Arthritis Res Ther 7: 12-19, 2005 https://doi.org/10.1186/ar1469
  12. MacRae TH. Structure and function of small heat shock/alpha- crystallin proteins: established concepts and emerging ideas. Cell Mol Life Sci 57: 899-913, 2000 https://doi.org/10.1007/PL00000733
  13. Moreau M, Brocheriou I, Petit L, Ninio E, Chapman MJ, Rouis M. Interleukin-8 mediates down-regulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque. Circulation 99: 420-426, 1999 https://doi.org/10.1161/01.CIR.99.3.420
  14. Perschinka H, Mayr M, Millonig G, Mayerl C, van der Zee R, Morrison SG, Morrison RP, Xu Q, Wick, G. Cross-reactive B-cell epitopes of microbial and human heat shock protein 60/65 in atherosclerosis. Arterioscler Thromb Vasc Biol 23: 1060-1065, 2003 https://doi.org/10.1161/01.ATV.0000071701.62486.49
  15. Peveri P, Walz A, Dewald B, Baggiolini M. A novel neutrophil- activating factor produced by human mononuclear phagocytes. J Exp Med 167: 1547-1559, 1988 https://doi.org/10.1084/jem.167.5.1547
  16. Pockley AG. Heat shock proteins as regulators of the immune response. Lancet 362: 469-476, 2003 https://doi.org/10.1016/S0140-6736(03)14075-5
  17. Pockley AG, Georgiades A, Thulin T, de Faire U, Frostegard J. Serum heat shock protein 70 levels predict the development of atherosclerosis in subjects with established hypertension. Hypertension 42: 235-238, 2003 https://doi.org/10.1161/01.HYP.0000086522.13672.23
  18. Rus HG, Vlaicu R, Niculescu F. Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall. Atherosclerosis 127: 263-271, 1996 https://doi.org/10.1016/S0021-9150(96)05968-0
  19. Schroder JM, Christophers E. Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol 142: 244-251, 1989
  20. Srivastava P. Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2, 185-194: 2002 https://doi.org/10.1038/nri749
  21. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915-924: 1989 https://doi.org/10.1056/NEJM198904063201407
  22. Tedgui A, Mallat, Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 86: 515-581, 2006 https://doi.org/10.1152/physrev.00024.2005
  23. Wang JM, Sica A, Peri G, Walter S, Padura IM, Libby P, Ceska M, Lindley I, Colotta F. Mantovani A. Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells. Arterioscler Thromb 11: 1166-1174, 1991 https://doi.org/10.1161/01.ATV.11.5.1166
  24. Whitley D, Goldberg SP, Jordan WD. Heat shock proteins: a review of the molecular chaperones. J Vasc Surg 29: 748-751, 1999 https://doi.org/10.1016/S0741-5214(99)70329-0
  25. Wick G, Perschinka H, Millonig G. Atherosclerosis as an autoimmune disease: an update. Trends Immunol 22: 665-669, 2001 https://doi.org/10.1016/S1471-4906(01)02089-0
  26. Wu YM, Robinson DR, Kung HJ. Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in prostate cancer cells. Cancer Res 64: 7311-7320, 2004 https://doi.org/10.1158/0008-5472.CAN-04-0972
  27. Yang X, Coriolan D, Murthy V, Schultz K, Golenbock DT, Beasley D. Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling. Am J Physiol Heart Circ Physiol 289: H1069-1076, 2005 https://doi.org/10.1152/ajpheart.00143.2005
  28. Yang X, Murthy V, Schultz K, Tatro JB, Fitzgerald KA, Beasley D. Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 291: H2334-2343, 2006 https://doi.org/10.1152/ajpheart.00252.2006
  29. Yue TL, Wang X, Sung CP, Olson B, McKenna PJ, Gu JL, Feuerstein GZ. Interleukin-8. A mitogen and chemoattractant for vascular smooth muscle cells. Circ Res 75: 1-7, 1994 https://doi.org/10.1161/01.RES.75.1.1