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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)
  • Received : 2010.03.23
  • Accepted : 2010.04.13
  • Published : 2010.04.30
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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.

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References

  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 https://doi.org/10.1111/j.0105-2896.2004.00201.x
  3. Vosshenrich CA, Di Santo JP: Cytokines: IL-21 joins the gamma (c)-dependent network? Curr Biol 11;R175-177, 2001 https://doi.org/10.1016/S0960-9822(01)00087-2
  4. 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 https://doi.org/10.1016/j.cytogfr.2007.04.003
  5. 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 https://doi.org/10.1021/bi0202023
  6. 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 https://doi.org/10.4049/jimmunol.177.6.3721
  7. 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 https://doi.org/10.1182/blood-2006-10-054973
  8. 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 https://doi.org/10.1073/pnas.200360997
  9. 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 https://doi.org/10.1038/35040504
  10. 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 https://doi.org/10.1189/jlb.0308149
  11. 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
  12. 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 https://doi.org/10.1002/art.22452
  13. 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 https://doi.org/10.1038/nrd2482
  14. Terman BI, Stoletov KV: VEGF and tumor angiogenesis. Einstein Quart J Biol 18;59-66, 2001
  15. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1;27-31, 1995 https://doi.org/10.1038/nm0195-27
  16. 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 https://doi.org/10.1084/jem.176.5.1375
  17. 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 https://doi.org/10.1084/jem.180.3.1141
  18. 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 https://doi.org/10.1111/1523-1747.ep12606974
  19. 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 https://doi.org/10.1038/sj.bjp.0701436
  20. 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 https://doi.org/10.1084/jem.188.6.1039
  21. 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 https://doi.org/10.1182/blood-2007-09-113878
  22. Griswold DE, Tzimas MN: Ultraviolet B-induced inflammatory cytokine production, in vivo: initial pharmacological characterization. Inflamm Res 44(Suppl 2);S209-210, 1995 https://doi.org/10.1007/BF01778337
  23. 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 https://doi.org/10.1111/1523-1747.ep12371677
  24. 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 https://doi.org/10.1046/j.1523-1747.1998.00378.x
  25. 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 https://doi.org/10.1111/j.1365-2133.2005.06368.x
  26. Nickoloff BJ, Qin JZ, Nestle FO: Immunopathogenesis of psoriasis. Clin Rev Allergy Immunol 33;45-56, 2007 https://doi.org/10.1007/s12016-007-0039-2
  27. 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
  28. 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 https://doi.org/10.1016/j.cellbi.2008.08.011
  29. 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 https://doi.org/10.1038/nature05969
  30. 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
  31. 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 https://doi.org/10.1074/jbc.271.36.21793
  32. 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 https://doi.org/10.1172/JCI27727

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