Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China.
Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China.
J Dermatol Sci. 2014 Feb;73(2):110-6. doi: 10.1016/j.jdermsci.2013.09.005. Epub 2013 Sep 25.
Interleukin-33 (IL-33) was recently recognized as a member of the IL-1 cytokine family. The triggers no matter environmental or endogenous that provoke IL-33 cellular release may be associated with inflammation, infection or tissue damage. However, to date, the regulatory role of IL-33 in the control of melanogenesis has not been elucidated.
The present study was designed to investigate the effect of IL-33 on melanogenesis and to explore its underlying mechanisms.
Melanocytes were exposed to IL-33. Then cell viabilities were measured by MTT assay. The improving activities of IL-33 were examined by melanin synthesis, tyrosinase (TYR) activity assay. The expressions of relative proteins were assessed by Western blotting.
IL-33 increased the TYR activity and melanin content in a dosage-dependent manner at concentrations of 1-10ng/ml. Treatment with 10ng/ml of IL-33 enhanced the expression of microphthalmia-associated transcription factor (MITF), TYR, tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT) in normal human foreskin-derived epidermal melanocytes (NHEM). Furthermore, IL-33 could remarkably promote the phosphorylation levels of p38 mitogen-activated protein kinases (MAPKs) and cyclic AMP-responsive element-binding protein (CREB). This pro-melanogenic effect could be partially reversed by the pre-treatment with the special p38 MAPK inhibitor, SB203580, and protein kinase A (PKA) inhibitor, H89.
Our results collectively indicated that IL-33 improved melanin biosynthesis in NHEM. This function might be attributed to the fact that IL-33 stimulates the phosphorylation of p38 MAPK and CREB, increases the TYR, TRP-1 and DCT expression through MITF, finally resulting in the augment of melanogenesis.
白细胞介素-33 (IL-33) 最近被认为是白细胞介素-1 细胞因子家族的一员。无论环境还是内源性触发细胞释放 IL-33 的因素都可能与炎症、感染或组织损伤有关。然而，迄今为止，IL-33 对黑色素生成的调控作用尚未阐明。
本研究旨在探讨 IL-33 对黑色素生成的影响及其潜在机制。
用 IL-33 处理黑素细胞。然后通过 MTT 法测定细胞活力。通过黑色素合成、酪氨酸酶 (TYR) 活性测定来检测 IL-33 的改善活性。通过 Western blot 法评估相关蛋白的表达。
IL-33 在 1-10ng/ml 浓度范围内呈剂量依赖性地增加 TYR 活性和黑色素含量。用 10ng/ml 的 IL-33 处理可增强正常人胚皮衍生表皮黑素细胞 (NHEM) 中小眼畸形相关转录因子 (MITF)、TYR、酪氨酸酶相关蛋白 1 (TRP-1) 和多巴色素互变异构酶 (DCT) 的表达。此外，IL-33 可显著促进 p38 丝裂原活化蛋白激酶 (MAPKs) 和环磷酸腺苷反应元件结合蛋白 (CREB) 的磷酸化水平。这种促黑色素生成作用可部分被 p38 MAPK 特异性抑制剂 SB203580 和蛋白激酶 A (PKA) 抑制剂 H89 预处理逆转。
我们的结果表明，IL-33 可改善 NHEM 中的黑色素生物合成。这一功能可能归因于 IL-33 通过 MITF 刺激 p38 MAPK 和 CREB 的磷酸化，增加 TYR、TRP-1 和 DCT 的表达，最终导致黑色素生成增加。
