紫外线诱导角质形成细胞炎症反应信号传导机制研究进展

摘要/Abstract

摘要：

紫外线（UV）是一种可以导致皮炎、光老化和癌变的重要的环境因子，UV诱导表皮角质形成细胞炎症因子的生成是上述疾病发生的重要分子事件。UV诱导角质形成细胞炎症涉及多种受体、细胞内信号传导相关调控分子和核转录因子的参与，主要包括表皮生长因子受体、芳香烃受体、过氧化物酶体增生物激活受体、蛋白激酶C家族、蛋白激酶B、丝裂原活化蛋白激酶家族、核转录因子κB和转录因子激活蛋白等，构成了复杂的炎症信号传导网络。

Abstract:

Li Li, Chen Xu, Gu Heng Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China Corresponding author: Gu Heng, Email: guheng@aliyun.com 【Abstract】 Ultraviolet （UV） is a kind of important environmental factor that can cause dermatitis, photoaging and skin cancerization. The UV-induced production of inflammatory factors by epidermal keratinocytes has been deemed an important molecular event in occurrence of the above diseases. Various receptors, intracellular signal transduction-related regulatory molecules and nuclear transcription factors are involved in UV-induced inflammatory responses in keratinocytes, which mainly include epidermal growth factor receptor, aryl hydrocarbon receptor, peroxisome proliferator-activated receptor, protein kinase C family, protein kinase B, mitogen-activated protein kinase family, nuclear factor-κB and transcription factor activator protein-1, etc, and constitute a complex inflammatory signal transduction network.

李莉陈旭顾恒. 紫外线诱导角质形成细胞炎症反应信号传导机制研究进展[J]. 中华皮肤科杂志, 2016, 49(2): 140-143.doi:

参考文献 41

［1］	de Gruijl FR. Photocarcinogenesis: UVA vs UVB［J］. Methods Enzymol, 2000, 319: 359⁃366.
［2］	Kabuyama Y, Homma MK, Kurosaki T, et al. Early signaling events induced by 280⁃nm UV irradiation［J］. Eur J Biochem, 2002, 269（2）: 664⁃670. DOI: 10.1046/j.0014⁃2956.2001.02698.x.
［3］	Fisher GJ, Kang S, Varani J, et al. Mechanisms of photoaging and chronological skin aging［J］. Arch Dermatol, 2002, 138（11）: 1462⁃1470. DOI: 10.1001/archderm.138.11.1462.
［4］	Quan T, Qin Z, Xia W, et al. Matrix⁃degrading metalloproteinases in photoaging［J］. J Investig Dermatol Symp Proc, 2009, 14（1）: 20⁃24. DOI: 10.1038/jidsymp.2009.8.
［5］	Clydesdale GJ, Dandie GW, Muller HK. Ultraviolet light induced injury: immunological and inflammatory effects［J］. Immunol Cell Biol, 2001, 79（6）: 547⁃568. DOI: 10.1046/j.1440⁃1711.2001.01047.x.
［6］	Wilgus TA, Koki AT, Zweifel BS, et al. Inhibition of cutaneous ultraviolet light B⁃mediated inflammation and tumor formation with topicalcelecoxib treatment［J］. Mol Carcinog, 2003, 38（2）: 49⁃58. DOI: 10.1002/mc.10141.
［7］	Meeran SM, Punathil T, Katiyar SK. IL⁃12 deficiency exacerbates inflammatory responses in UV⁃irradiated skin and skin tumors［J］. J Invest Dermatol, 2008, 128（11）: 2716⁃2727. DOI: 10.1038/jid.2008.140.
［8］	Zheng D, Bode AM, Zhao Q, et al. The cannabinoid receptors are required for ultraviolet⁃induced inflammation and skin cancer⁃development［J］. Cancer Res, 2008, 68（10）: 3992⁃3998. DOI:10.1158/0008⁃5472.CAN⁃07⁃6594.
［9］	Strickland I, Rhodes LE, Flanagan BF, et al. TNF⁃alpha and IL⁃8 are upregulated in the epidermis of normal human skin after UVB exposure: correlation with neutrophil accumulation and E⁃selectin ［J］. J Invest Dermatol, 1997, 108（5）: 763⁃768. DOI: 10. 1111/1523⁃1747.ep12292156.
［10］	Luo D, Yaar M, Tsai A, et al. Solar⁃simulated irradiation evokes a persistent and biphasic IL⁃1alpha response［J］. Exp Dermatol, 2004, 13（1）: 11⁃17. DOI: 10.1111/j.0906⁃6705.2004.00102.x.
［11］	Naderi⁃Hachtroudi L, Peters T, Brenneisen P, et al. Induction of manganese superoxide dismutase in human dermal fibroblasts: a UV⁃B⁃mediated paracrine mechanism with the release of epidermal interleukin 1 alpha, interleukin 1 beta, and tumor necrosis factor alpha［J］. Arch Dermatol, 2002, 138（11）: 1473⁃1479.
［12］	Shin SW, Jung E, Kim S, et al. Antagonizing effects and mechanisms of afzelin against UVB⁃induced cell damage［J/OL］. PLoS One, 2013, 8（4）: e61971 ［2013⁃04⁃22］. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061971. DOI: 10.1371/ journal.pone.0061971.
［13］	Xu Y, Shao Y, Voorhees JJ, et al. Oxidative inhibition of receptor⁃type protein⁃tyrosine phosphatase kappa by ultraviolet irradiation activates epidermal growth factor receptor in human keratinocytes［J］. J Biol Chem, 2006, 281（37）: 27389⁃27397. DOI: 10.1074/jbc. M602355200.
［14］	Xu Y, Shao Y, Zhou J. Ultraviolet irradiation⁃induces epidermal growth factor receptor （EGFR） nuclear translocation in human keratinocytes［J］. J Cell Biochem, 2009, 107（5）: 873⁃880. DOI: 10. 1002/jcb.22195.
［15］	Lee KM, Lee KW, Jung SK, et al. Kaempferol inhibits UVB⁃induced COX⁃2 by suppressing Src kinase activity［J］. Biochem Pharmacol, 2010, 80（12）: 2042⁃2049. DOI: 10.1016/j.bcp.2010.06.042.
［16］	Fritsche E, Schäfer C, Calles C, et al. Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatictarget for ultraviolet B radiation［J］. Proc Natl Acad Sci U S A, 2007, 104（21）: 8851⁃8856. DOI: 10.1073/pnas.0701764104.
［17］	El⁃Abaseri TB, Putta S, Hansen LA. Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activationof the epidermal growth factor receptor［J］. Carcinogenesis, 2006, 27（2）: 225⁃231. DOI: 10.1093/carcin/bgi220.
［18］	Warmuth I, Harth Y, Matsui MS, et al. Ultraviolet radiation induces phosphorylation of the epidermal growth factor receptor［J］. Cancer Res, 1994, 54（2）: 374⁃376.
［19］	Kuenzli S, Saurat JH. Peroxisome proliferator⁃activated receptors in cutaneous biology［J］. Br J Dermatol, 2003, 149（2）: 229⁃236. DOI: 10.1046/j.1365⁃2133.2003.05532.x.
［20］	Yoshizaki N, Fujii T, Masaki H, et al. Orange peel extract, containing high levels of polymethoxyflavonoid, suppressed UVB⁃induced COX⁃2 and PGE2 production in HaCaT cells through PPAR⁃γ activation［J］. Exp Dermatol, 2014, Suppl 1: 18⁃22. DOI: 10.1111/exd.12394.
［21］	Kippenberger S, Loitsch SM, Grundmann⁃Kollmann M, et al. Activators of peroxisome proliferator⁃activated receptors protect human skin from ultraviolet⁃B⁃light⁃induced inflammation［J］. J Invest Dermatol, 2001, 117（6）: 1430⁃1436. DOI: 10.1046/j.0022⁃202x.2001.01537.x.
［22］	Park MH, Park JY, Lee HJ, et al. The novel PPAR α/γ dual agonist MHY 966 modulates UVB⁃induced skin inflammation by inhibiting NF⁃κBactivity［J/OL］. PLoS One, 2013, 8（10）: e67820 ［2013⁃10⁃09］. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076820. DOI: 10.1371/journal.pone.0076820.
［23］	Montagner A, Delgado MB, Tallichet⁃Blanc C, et al. Src is activated by the nuclear receptor peroxisome proliferator⁃activated receptor β/δ in ultraviolet radiation⁃induced skin cancer［J］. EMBO Mol Med, 2014, 6（1）: 80⁃98. DOI: 10.1002/emmm.201302666.
［24］	Cataisson C, Joseloff E, Murillas R, et al. Activation of cutaneous protein kinase C alpha induces keratinocyte apoptosis and intraepidermal inflammation by independent signaling pathways［J］. J Immunol, 2003, 171（5）: 2703⁃2713. DOI: 10.4049/jimmunol.171.5.2703.
［25］	Lim TG, Kim JE, Lee SY, et al. The daidzein metabolite, 6,7,4′⁃Trihydroxyisoflavone, is a novel inhibitor of PKCα in suppressing solarUV⁃induced matrix metalloproteinase 1［J］. Int J Mol Sci, 2014, 15（11）: 21419⁃21432. DOI: 10.3390/ijms151121419.
［26］	Rhee SG. Regulation of phosphoinositide⁃specific phospholipase C［J］. Annu Rev Biochem, 2001, 70: 281⁃312. DOI: 10.1146/annurev. biochem.70.1.281.
［27］	Bunney TD, Katan M. Phospholipase C epsilon: linking second messengers and small GTPases［J］. Trends Cell Biol, 2006, 16（12）: 640⁃648. DOI: 10.1016/j.tcb.2006.10.007.
［28］	Huang C, Ma Wy, Bowden GT, et al. Ultraviolet B⁃induced activated protein⁃1 activation does not require epidermal growth factor receptor but is blocked by a dominant negative PKClambda/iota［J］. J Biol Chem, 1996, 271（49）: 31262⁃31268.
［29］	Huang C, Ma W, Dong Z. Signal transduction through atypical PKCs, but not the EGF receptor, is necessary for UVC⁃induced AP⁃1 activation in immortal murine cells［J］. Oncogene, 1997, 14（16）: 1945⁃1954. DOI: 10.1038/sj.onc.1201056.
［30］	Huang C, Li J, Chen N, et al. Inhibition of atypical PKC blocks ultraviolet⁃induced AP⁃1 activation by specifically inhibiting ERKsactivation［J］. Mol Carcinog, 2000, 27（2）: 65⁃75.
［31］	Arun SN, Kaddour⁃Djebbar I, Shapiro BA, et al. Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes［J］. Oncogene, 2011, 30（13）: 1586⁃1596.DOI: 10.1038/onc.2010.540.
［32］	Tang Q, Gonzales M, Inoue H, et al. Roles of Akt and glycogen synthase kinase 3beta in the ultraviolet B induction of cyclooxygenase⁃2 transcription in human keratinocytes［J］. Cancer Res, 2001, 61（11）: 4329⁃4332.
［33］	Remy G, Risco AM, Iñesta⁃Vaquera FA, et al. Differential activation of p38MAPK isoforms by MKK6 and MKK3［J］. Cell Signal, 2010, 22（4）: 660⁃667. DOI: 10.1016/j.cellsig.2009.11.020.
［34］	Whitmarsh AJ, Davis RJ. Role of mitogen⁃activated protein kinase kinase 4 in cancer［J］. Oncogene, 2007, 26（22）: 3172⁃3184. DOI:10.1038/sj.onc.1210410.
［35］	Lang R, Hammer M, Mages J. DUSP meet immunology: dual specificity MAPK phosphatases in control of the inflammatory response［J］. J Immunol, 2006, 177（11）: 7497⁃7504. DOI: 10.4049/jimmunol.177.11.7497.
［36］	Lee JW, Ryu HC, Ng YC, et al. 12（S）⁃Hydroxyheptadeca⁃5Z,8E,10E⁃trienoic acid suppresses UV⁃induced IL⁃6 synthesis in keratinocytes, exerting an anti⁃inflammatory activity［J］. Exp Mol Med, 2012, 44（6）: 378⁃386. DOI: 10.3858/emm.2012.44.6.043.
［37］	Zhu F, Zykova TA, Kang BS, et al. Bidirectional signals transduced by TOPK⁃ERK interaction increase tumorigenesis of HCT116 colorectal cancer cells［J］. Gastroenterology, 2007, 133（1）: 219⁃231. DOI: 10.1053/j.gastro.2007.04.048.
［38］	王平, 毕志刚, 许爱娥, 等. 中波紫外线辐射对人表皮角质形成细胞核因子κB转录活性的影响［J］. 中华皮肤科杂志, 2006, 39（9）: 518⁃520. DOI: 10.3760/j.issn:0412⁃4030.2006.09.009.
	Wang P, Bi ZG, Xu AE, et al. Effect of ultraviolet B irradiation on the transcriptional activity of nuclear factor κB in human epidermal keratinocytes［J］. Chin J Dermatol, 2006, 39（9）: 518⁃520. DOI:10.3760/j.issn:0412⁃4030.2006.09.009.
［39］	丁兰, 陈旭, 徐松, 等. 中波紫外线对角质形成细胞NF⁃κB p65及其抑制因子IκBα表达的影响［J］. 中华皮肤科杂志, 2014, 47 （11）: 780⁃784. DOI: 10.3760/cma.j.issn.0412⁃4030.2014.011.004.
	Ding L, Chen X, Xu S, et al. Effects of ultraviolet B on the s of nuclear factor⁃κB p65 and its inhibitory factor IκBα in keratinocytes［J］. Chin J Dermatol, 2014, 47（11）: 780⁃784. DOI: 10.3760/cma.j.issn.0412⁃4030.2014.011.004.
［40］	Kim AL, Labasi JM, Zhu Y, et al. Role of p38 MAPK in UVB⁃induced inflammatory responses in the skin of SKH⁃1 hairless mice［J］. J Invest Dermatol, 2005, 124（6）: 1318⁃1325. DOI: 10.1111/j.0022⁃202X.2005.23747.x.
［41］	Chang EJ, Kundu JK, Liu L, et al. Ultraviolet B radiation activates NF⁃κB and induces iNOS in HR⁃1 hairless mouse skin: role of IκB kinase⁃β［J］. Mol Carcinog, 2011, 50（4）: 310⁃317. DOI: 10.1002/mc.20646.