Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease characterized by detachment of keratinocytes (acantholysis). It has been proposed that PV IgG might trigger signaling and that this process may lead to acantholysis. Indeed, we recently identified a rapid and dose-dependent phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and heat shock protein (HSP) 27 after binding of PV antibodies to cultured keratinocytes. In human keratinocyte cultures, inhibitors of p38MAPK prevented PV IgG-induced phosphorylation of HSP27 and, more importantly, prevented the early cytoskeletal changes associated with loss of cell-cell adhesion. This study was undertaken to (i) determine whether p38MAPK and HSP25, the murine HSP27 homolog, were similarly phosphorylated in an in vivo model of PV and (ii) investigate the potential therapeutic use of p38MAPK inhibition to block blister formation in an animal model of PV. We now report that p38MAPK inhibitors prevented PV blistering disease in vivo. Targeting the end-organ by inhibiting keratinocyte desmosome signaling may be effective for treating desmosome autoimmune blistering disorders.

译文

寻常型天疱疮 (PV) 是一种威胁生命的自身免疫性水疱性皮肤病,其特征是角质形成细胞脱离 (棘皮松解)。已经提出PV IgG可能触发信号传导,并且该过程可能导致棘层分解。实际上,我们最近确定了PV抗体与培养的角质形成细胞结合后,p38丝裂原活化蛋白激酶 (p38MAPK) 和热休克蛋白 (HSP) 27的快速且剂量依赖性磷酸化。在人角质形成细胞培养物中,p38MAPK抑制剂阻止了PV IgG诱导的HSP27磷酸化,更重要的是,阻止了与细胞间粘附丧失相关的早期细胞骨架变化。进行这项研究是为了 (i) 确定p38MAPK和HSP25 (鼠HSP27同源物) 在PV的体内模型中是否被类似地磷酸化,以及 (ii) 研究p38MAPK抑制在阻止水疱形成中的潜在治疗用途。PV的动物模型。我们现在报道p38MAPK抑制剂在体内预防了PV起泡病。通过抑制角质形成细胞桥粒信号传导靶向终末器官可能对治疗桥粒自身免疫性水疱性疾病有效。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录