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http://dx.doi.org/10.4110/in.2010.10.2.76

The Production IL-21 and VEGF in UVB-irradiated Human Keratinocyte Cell Line, HaCaT  

Kim, Hye-Min (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Kang, Jae-Seung (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Lee, Wang-Jae (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Publication Information
IMMUNE NETWORK / v.10, no.2, 2010 , pp. 76-81 More about this Journal
Abstract
Ultraviolet B (UVB) induces multiple inflammatory and carcinogenic reactions. In skin, UVB induces to secrete several kinds of inflammatory cytokines from keratinocytes and also increases angiogenic process via the modulation of vascular endothelial growth factor (VEGF) production. Interleukin-21 (IL-21) is an inflammatory cytokine and produced by activated T cells. The biologic functions of IL-21 have not yet extensively studied. In the present study, we investigate the production of IL-21 from human keratinocyte cell line, HaCaT and its biological effect after exposure to UVB. First, we confirmed the IL-21 production and its receptor expression in HaCaT. And then, the change of IL-21 and VEGF production in HaCaT by UVB irradiation was examined. Not only IL-21 but also VEGF production was enhanced by UVB irradiation. Next, to determine relationship of enhanced production of IL-21 and VEGF, we detected VEGF production after neutralization of IL-21. VEGF production was reduced by IL-21 neutralization, which indicates that the IL-21 is involved in the VEGF production. Taken together, our results suggest that IL-21 and VEGF production is enhanced by UVB irradiation in HaCaT. In addition, it seems that IL-21 plays a role in the angiogenic process in skin via the modulation of VEGF production.
Keywords
HaCaT; UVB; IL-21; VEGF;
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1 Leonard WJ, Spolski R: Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol 5;688-698, 2006
2 Mehta DS, Wurster AL, Grusby MJ: Biology of IL-21 and the IL-21 receptor. Immunol Rev 202;84-95, 2004   DOI   ScienceOn
3 Sakkoula E, Pipili-Synetos E, Maragoudakis ME: Involvement of nitric oxide in the inhibition of angiogenesis by interleukin-2. Br J Pharmacol 122;793-795, 1997   DOI   ScienceOn
4 Volpert OV, Fong T, Koch AE, Peterson JD, Waltenbaugh C, Tepper RI, Bouck NP: Inhibition of angiogenesis by interleukin 4. J Exp Med 188;1039-1046, 1998   DOI   ScienceOn
5 Castermans K, Tabruyn SP, Zeng R, van Beijnum JR, Eppolito C, Leonard WJ, Shrikant PA, Griffioen AW: Angiostatic activity of the antitumor cytokine interleukin-21. Blood 112;4940-4947, 2008   DOI   ScienceOn
6 Griswold DE, Tzimas MN: Ultraviolet B-induced inflammatory cytokine production, in vivo: initial pharmacological characterization. Inflamm Res 44(Suppl 2);S209-210, 1995   DOI
7 Kondo S, Kono T, Sauder DN, McKenzie RC: IL-8 gene expression and production in human keratinocytes and their modulation by UVB. J Invest Dermatol 101;690-694, 1993   DOI   ScienceOn
8 Bielenberg DR, Bucana CD, Sanchez R, Donawho CK, Kripke ML, Fidler IJ: Molecular regulation of UVB-induced cutaneous angiogenesis. J Invest Dermatol 111;864-872, 1998   DOI   ScienceOn
9 Yano K, Kadoya K, Kajiya K, Hong YK, Detmar M: Ultraviolet B irradiation of human skin induces an angiogenic switch that is mediated by upregulation of vascular endothelial growth factor and by downregulation of thrombospondin- 1. Br J Dermatol 152;115-121, 2005   DOI   ScienceOn
10 Nickoloff BJ, Qin JZ, Nestle FO: Immunopathogenesis of psoriasis. Clin Rev Allergy Immunol 33;45-56, 2007   DOI   ScienceOn
11 Monteleone G, Pallone F, Macdonald TT: Interleukin-21 (IL-21)-mediated pathways in T cell-mediated disease. Cytokine Growth Factor Rev 2;185-191, 2009
12 Suto A, Wurster AL, Riner SL, Grusby MJ: IL-21 inhibits IFN-gamma production in developing Th1 cells through the repression of Eomesodermin expression. J Immunol 177; 3721-3727, 2006   DOI
13 Vosshenrich CA, Di Santo JP: Cytokines: IL-21 joins the gamma (c)-dependent network? Curr Biol 11;R175-177, 2001   DOI   ScienceOn
14 Brandt K, Singh PB, Bulfone-Paus S, Ruckert R: Interleukin- 21: a new modulator of immunity, infection, and cancer. Cytokine Growth Factor Rev 18;223-232, 2007   DOI   ScienceOn
15 Habib T, senadheera S, Winberg K, Kaushansky K: The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry 41;8725-8731, 2002   DOI   ScienceOn
16 Zeng R, Spolski R, Casas E, Zhu W, Levy DE, Leonard WJ: The molecular basis of IL-21-mediated proliferation. Blood 109;4135-4142, 2007   DOI   ScienceOn
17 Ozaki K, Kikly K, Michalovich D, Young PR, Leonard WJ: Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proc Natl Acad Sci U S A 97; 11439-11444, 2000   DOI   ScienceOn
18 Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D: Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408;57-63, 2000   DOI   ScienceOn
19 Leonard WJ, Zeng R, Spolski R: Interleukin 21: a cytokine/ cytokine receptor system that has come of age. J Leukoc Biol 84;348-356, 2008   DOI   ScienceOn
20 Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, Kimura H: Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT. Cell Biol Int 32;1405-1411, 2008   DOI   ScienceOn
21 Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, Dong C: Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448;480-483, 2007   DOI   ScienceOn
22 Hirakawa S, Fujii S, Kajiya K, Yano K, Detmar M: Vascular endothelial growth factor promotes sensitivity to ultraviolet B-induced cutaneous photodamage. Blood 105;2392-2399, 2004
23 Brauchle M, Funk JO, Kind P, Werner S: Ultraviolet B and $H_2O_2$ are potent inducers of vascular endothelial growth factor expression in cultured keratinocytes. J Biol Chem 271;21793-21797, 1996   DOI   ScienceOn
24 Pesce J, Kaviratne M, Ramalingam TR, Thompson RW, Urban JF Jr, Cheever AW, Young DA, Collins M, Grusby MJ, Wynn TA: The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest 116;2044-2055, 2006   DOI   ScienceOn
25 Terman BI, Stoletov KV: VEGF and tumor angiogenesis. Einstein Quart J Biol 18;59-66, 2001
26 Sawalha AH, Kaufman KM, Kelly JA, Adler AJ, Aberle T, Kilpatrick J, Wakeland EK, Li QZ, Wandstrat AE, Karp DR, James JA, Merrill JT, Lipsky P, Harley JB: Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus. Ann Rheum Dis 67;458-461, 2008
27 Young DA, Hegen M, Ma HL, Whitters MJ, Albert LM, Lowe L, Senices M, Wu PW, Sibley B, Leathurby Y, Brown TP, Nickerson-Nutter C, Keith JC Jr, Collins M: Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum 56;1152-1163, 2007   DOI   ScienceOn
28 Skak K, Kragh M, Hausman D, Smyth MJ, Sivakumar PV: Interleukin 21: combination strategies for cancer therapy. Nat Rev Drug Discov 7;231-240, 2008   DOI   ScienceOn
29 Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1;27-31, 1995   DOI   ScienceOn
30 Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L: Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 176;1375-1379, 1992   DOI   ScienceOn
31 Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF: Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180;1141-1146, 1994   DOI   ScienceOn
32 Brown LF, Harrist TJ, Yeo KT, Stahle-Backdahl M, Jackman RW, Berse B, Tognazzi K, Dvorak HF, Detmar M: Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme. J Invest Dermatol 104;744-749, 1995   DOI   ScienceOn