武汉云克隆科技股份有限公司

Abstract:Pulmonary Staphylococcus aureus (SA) infections are a public health concern and a major complication of hyper-IgE syndrome, caused by mutations in STAT3. In contrast to previous findings of skin infection, we observed that clearance of SA from the lung did not require T, B, or NK cells but did require Stat3 activation. Immunohistochemistry showed robust Stat3 phosphorylation in the lung epithelium. We identified that a critical Stat3 target gene in lung epithelium is Reg3g (regenerating islet-derived 3 γ), a gene which is highly expressed in gastrointestinal epithelium but whose role in pulmonary host defense is uncharacterized. Stat3 regulated Reg3g transcription through direct binding at the Reg3g promoter region. Recombinant Reg3γ bound to SA and had both bacteriostatic and bactericidal activity in a dose-dependent fashion. Stat3 inhibition in vivo reduced Reg3g transcripts in the lung, and more importantly, recombinant Reg3γ rescued mice from defective SA clearance. These findings reveal an antibacterial function for lung epithelium through Stat3-mediated induction of Reg3γ.

摘要：信号传导转录激活因子3（STAT3）突变引起的肺金黄色葡萄球菌(SA)感染是一个公众健康问题，也是高IgE综合征的主要并发症。与以往的皮肤感染不同，清除肺金黄色葡萄球菌(SA)不需要T、B或NK细胞参与，但需要STAT3的活化作用。免疫组化试验显示肺上皮细胞有较强的STAT3磷酸化。在肺上皮细胞中一个关键的STAT3靶基因Reg3g被发现，它在胃肠道上皮中高度表达，但在肺宿主防御中的作用尚不明确。STAT3可以直接与Reg3g的启动子区结合参与调控Reg3g的转录过程。Reg3γ与SA重组结合，在一定剂量下具有抑菌性和杀菌性。STAT3体内抑制作用可以抑制肺部Reg3g的转录表达，更重要的是可以通过重组Reg3γ清除肺金黄色葡萄球菌(SA)来治疗小鼠。这些发现揭示了STAT3诱导再生胰岛衍生蛋白3γ表达在肺上皮的抗菌作用。

使用试剂原文信息：Reg3γ was detected in whole lung homogenate by sandwich ELISA (USCN Life Sciences) in accordance with the protocol provided with the kit.