Kanekura T, Higashi Y, Kanzaki T
Department of Dermatology, Faculty of Medicine, Kagoshima University, Japan.
J Rheumatol. 2001 Jul;28(7):1568-72.
We and others reported on the beneficial effects of combined therapy using 8-methoxypsoralen and long wave ultraviolet light (PUVA therapy) in the treatment of scleroderma. We now investigate the mechanism by which PUVA therapy is effective by comparing interleukin 1beta (IL-1beta) mediated signal transduction in scleroderma fibroblasts and those from normal skin.
Prostaglandin E2 (PGE2) production and expression of cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, and COX-2 (enzymes that regulate PGE2 production) were examined in untreated and IL-1beta treated fibroblasts from scleroderma involved and normal skin. The effect of UVA irradiation on enzyme expression and PGE2 production was examined. PGE2 was measured by a competitive radioimmunoassay and enzyme expression was analyzed by Western immunoblotting and Northern blotting.
Constitutive PGE2 production was significantly upregulated and IL-1beta induced PGE2 production was increased by the enhancing expression of both COX-2 mRNA and protein in fibroblasts from scleroderma involved skin; PGE2 production and COX-2 expression were inhibited by UVA irradiation.
Enhanced PGE2 production regulated by COX-2 expression in scleroderma fibroblasts may contribute to the development of this disorder. PUVA therapy might exhibit its beneficial effect, at least in part, by inhibiting COX-2 expression transcriptionally and translationally, with subsequent inhibition of PGE2 production.
我们及其他研究者报道了8-甲氧基补骨脂素与长波紫外线联合治疗（PUVA疗法）对硬皮病的有益效果。我们现在通过比较硬皮病成纤维细胞和正常皮肤成纤维细胞中白细胞介素1β（IL-1β）介导的信号转导，来研究PUVA疗法有效的机制。
检测未经处理和经IL-1β处理的硬皮病受累皮肤及正常皮肤的成纤维细胞中前列腺素E2（PGE2）的产生以及胞质磷脂酶A2（cPLA2）、环氧化酶（COX）-1和COX-2（调节PGE2产生的酶）的表达。检测紫外线A（UVA）照射对酶表达和PGE2产生的影响。通过竞争性放射免疫测定法测量PGE2，并通过蛋白质免疫印迹法和Northern印迹法分析酶表达。
在硬皮病受累皮肤的成纤维细胞中，COX-2 mRNA和蛋白质表达增强，导致组成性PGE2产生显著上调，且IL-1β诱导的PGE2产生增加；UVA照射抑制了PGE2产生和COX-2表达。
硬皮病成纤维细胞中由COX-2表达调节的PGE2产生增强可能促成了这种疾病的发展。PUVA疗法可能至少部分通过转录和翻译水平抑制COX-2表达，随后抑制PGE2产生而发挥其有益作用。
