姜黄素通过 MAPK 通路防止高渗诱导的人角膜上皮细胞中 IL-1β的升高。
Curcumin protects against hyperosmoticity-induced IL-1beta elevation in human corneal epithelial cell via MAPK pathways.
机构信息
Tissue Culture Center, Department of Pathology, New York Eye and Ear Infirmary, 310 E. 14th Street, New York, NY 10003, USA.
出版信息
Exp Eye Res. 2010 Mar;90(3):437-43. doi: 10.1016/j.exer.2009.12.004. Epub 2009 Dec 23.
Increased tear osmolarity is an essential feature of dry eye disease. Curcumin, a natural polyphenol extracted from herb turmeric, has recently been reported to have anti-inflammatory effects. However, its anti-inflammatory effects have not been investigated in dry eye disease. It has been reported that elevated osmolarity achieved by adding sodium chloride to the culture medium of corneal epithelial cells increased the production of IL-1beta, a proinflammation cytokine. This in vitro dry eye model was used to test the anti-inflammatory effects of curcumin. In the present study, a 450 mOsM hyperosmotic medium was produced by adding sodium chloride to the culture medium to reach a final concentration of 90mM. Human corneal epithelial cells cultured in this hyperosmotic medium for 24h showed an increase of IL-1beta, IL-6 and TNF-alpha levels in the conditioned medium. IL-1beta was also upregulated at mRNA levels. Activation of p38 MAP kinase (p38), JNK MAP kinase (JNK) and NF-kappaB in cultured corneal epithelial cells were also induced by hyperosmotic conditions. Curcumin at concentrations of 1-30muM did not affect the cell viability of cultured corneal epithelial cells. Pretreatment of curcumin (5muM) completely abolished the increased production of IL-1beta induced by the hyperosmotic medium. Increased phosphorylation of p38 caused by high osmolarity was also completely abolished by curcumin, whereas the phosphorylation of JNK was only partially inhibited. SB 203580 (p38 inhibitor), but not SP 600125 (JNK inhibitor), completely suppressed hyperosmoticity-induced IL-1beta production, indicating that the inhibition of production of IL-1beta by curcumin may be achieved through the p38 signal pathway. Curcumin completely abolished a hyperosmoticity-induced increase of NF-kappaB p65. NF-kappaB inhibitor suppressed hyperosmoticity-induced IL-1beta production. p38 inhibitor suppressed hyperosmoticity-induced NF-kappaB activation, indicating that NF-kappaB activation was dependent on p38 activation. The present study suggests that curcumin might have therapeutic potential for treating dry eye disease.
泪液渗透压升高是干眼症的一个基本特征。姜黄素是从草药姜黄中提取的一种天然多酚，最近有报道称其具有抗炎作用。然而，它在干眼症中的抗炎作用尚未得到研究。据报道，通过在角膜上皮细胞的培养基中添加氯化钠来提高渗透压，会增加促炎细胞因子白细胞介素-1β（IL-1β）的产生。本研究采用这种体外干眼症模型来测试姜黄素的抗炎作用。在本研究中，通过在培养基中添加氯化钠来制备 450mOsM 的高渗培养基，使其最终浓度达到 90mM。将人角膜上皮细胞在这种高渗培养基中培养 24 小时后，发现条件培养基中 IL-1β、IL-6 和 TNF-α水平升高。IL-1β 的 mRNA 水平也上调。高渗条件还诱导培养的角膜上皮细胞中 p38 MAP 激酶（p38）、JNK MAP 激酶（JNK）和 NF-κB 的激活。浓度为 1-30μM 的姜黄素不影响培养的角膜上皮细胞的细胞活力。姜黄素（5μM）预处理完全消除了高渗培养基诱导的 IL-1β产生增加。高渗透压引起的 p38 磷酸化也被姜黄素完全消除，而 JNK 的磷酸化仅部分抑制。SB 203580（p38 抑制剂），而不是 SP 600125（JNK 抑制剂），完全抑制了高渗诱导的 IL-1β 产生，表明姜黄素抑制 IL-1β 的产生可能是通过 p38 信号通路实现的。姜黄素完全消除了高渗透压诱导的 NF-κB p65 增加。NF-κB 抑制剂抑制高渗诱导的 IL-1β 产生。p38 抑制剂抑制高渗诱导的 NF-κB 激活，表明 NF-κB 激活依赖于 p38 激活。本研究表明，姜黄素可能具有治疗干眼症的潜力。
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