The Production IL-21 and VEGF in UVB-irradiated Human Keratinocyte Cell Line, HaCaT
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초록
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-21but 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.
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-21but 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.
참고문헌 (32)
- Leonard WJ, "Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation", Nat Rev Immunol, 5, pp.688~698 (2006)
- Mehta DS, "Biology of IL-21 and the IL-21 receptor", Immunol Rev, 202, pp.84~95 (2004)
- Vosshenrich CA, "Cytokines: IL-21 joins the gamma (c)-dependent network?", Curr Biol, 11, pp.R175~R177 (2001)
- Brandt K, "Interleukin- 21: a new modulator of immunity, infection, and cancer", Cytokine Growth Factor Rev, 18, pp.223~232 (2007)
- Habib T, "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, pp.8725~8731 (2002)
- Suto A, "IL-21 inhibits IFN-gamma production in developing Th1 cells through the repression of Eomesodermin expression", J Immunol, 177, pp.3721~3227 (2006)
- Zeng R, "The molecular basis of IL-21-mediated proliferation", Blood, 109, pp.4135~4142 (2007)
- Ozaki K, "Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain", Proc Natl Acad Sci U S A, 97, pp.11439~11444 (2000)
- Parrish-Novak J, "Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function", Nature, 408, pp.57~63 (2000)
- Leonard WJ, "Interleukin 21: a cytokine", cytokine receptor system that has come of age, 2008, pp.84, 348~356
- Sawalha AH, "Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus", Ann Rheum Dis, 67, pp.458~461 (2008)
- Young DA, "Blockade of the interleukin-21", interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis, 2007, pp.56, 1152~1163
- Skak K, "Interleukin 21: combination strategies for cancer therapy", Nat Rev Drug Discov, 7, pp.231~240 (2008)
- Terman BI, "VEGF and tumor angiog", Einstein Quart J Biol, 18, pp.59~66 (2001)
- Folkman J, "Angiogenesis in cancer, vascular, rheumatoid and other disease", Nat Med, 1, pp.27~31 (1995)
- Brown LF, "Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing", J Exp Med, 176, pp.1375~1379 (1992)
- Detmar M, "Overexpression of vascular permeability factor", vascular endothelial growth factor and its receptors in psoriasis, 1994, pp.180, 1141~1146
- Brown LF, "Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme", J Invest Dermatol, 104, pp.744~749 (1995)
- Sakkoula E, "Involvement of nitric oxide in the inhibition of angiogenesis by interleukin-2", Br J Pharmacol, 122, pp.793~795 (1997)
- Volpert OV, "Inhibition of angiogenesis by interleukin 4", J Exp Med, 188, pp.1039~1046 (1998)
- Castermans K, "Angiostatic activity of the antitumor cytokine interleukin-21", Blood, 112, pp.4940~4947 (2008)
- Griswold DE, "Ultraviolet B-induced inflammatory cytokine production, in vivo: initial pharmacological characterization", Inflamm Res, 44(2), pp.S209~S210 (1995)
- Kondo S, "IL-8 gene expression and production in human keratinocytes and their modulation by UVB", J Invest Dermatol, 101, pp.690~694 (1993)
- Bielenberg DR, "Molecular regulation of UVB-induced cutaneous angiogenesis", J Invest Dermatol, 111, pp.864~872 (1998)
- Yano K, "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, pp.115~121 (2005)
- Nickoloff BJ, "Immunopathogenesis of psoriasis", Clin Rev Allergy Immunol, 33, pp.45~56 (2007)
- Monteleone G, "Interleukin-21 (IL-21)-mediated pathways in T cell-mediated disease", Cytokine Growth Factor Rev, 2, pp.185~191 (2009)
- Yoshizumi M, "Release of cytokines", chemokinesand cell death in UVB-irradiated human keratinocytes, HaCaT, 2008, pp.32, 1405~1411
- Nurieva R, "Essential autocrine regulation by IL-21 in the generation of inflammatory T cells", Nature, 448, pp.480~483 (2007)
- Hirakawa S, "Vascular endothelial growth factor promotes sensitivity to ultraviolet B-induced cutaneous photodamage", Blood, 105, pp.2392~2399 (2004)
- Brauchle M, "Ultraviolet B and H2O2 are potent inducers of vascular endothelial growth factor expression in cultured keratinocytes", J Biol Chem, 271, pp.21793~21797 (1996)
- Pesce J, "The IL-21 receptor augments Th2 effector function and alternative macrophage activation", J Clin Invest, 116, pp.2044~2055 (2006)