Development of new drugs based on molecular mechanism for infectious corneal ulcer

角膜基质中的胶原降解与角膜溃疡的病因有关。此外，角膜成纤维细胞部分通过介导胶原降解而参与角膜基质中胶原的重塑。角膜结构受性激素状态的影响，我们研究了性激素对角膜成纤维细胞胶原降解的影响。17β-雌二醇和孕酮，女性性激素，抑制白介素1-β诱导的胶原降解，而睾酮和脱氢表雄酮则无此作用。IL-1β可抑制角膜成纤维细胞中基质金属蛋白酶的表达和活化，抑制IL-1β诱导的p38 MAPK的磷酸化，而不影响MAPKs ERK或JNK的磷酸化。17β-雌二醇也抑制IL-1β诱导的IkappaB-α的磷酸化。女性性激素可抑制IL-1β刺激的角膜成纤维细胞中基质金属蛋白酶的表达和活性，从而抑制这些细胞的胶原降解。

Collagen degradation of corneal stroma relates to the etiology of corneal ulcerration.Moreover,Corneal fibroblasts contribute to collagen remodeling in the corneal stroma in part by mediating collagen degradation.Corneal structure is influenced by sex hormone status,we examined the effects of sex hormones on collagen degradation by corneal fibroblasts.17beta-Estradiol and progesterone,female sex hormones,inhibited interleukin (IL)-1beta-induced collagen degradation,whereas testosterone and DHEA had no such effect.MMP expression and activation in corneal fibroblasts exposed to IL-1beta were also inhibited by them.They nhibited the IL-1beta-induced phosphorylation of p38 MAPK without affecting that of the MAPKs ERK or JNK.17beta-Estradiol also inhibited the IL-1beta-induced phosphorylation of IkappaB-alpha.Female sex hormones inhibited MMP expression and activity in IL-1beta-stimulated corneal fibroblasts and thereby suppressed collagen degradation by these cells.