TIPE2 Suppresses Pseudomonas aeruginosa Keratitis by Inhibiting NF-κB Signaling and the Infiltration of Inflammatory Cells
TIPE2 Suppresses Pseudomonas aeruginosa Keratitis by Inhibiting NF-κB Signaling and the Infiltration of Inflammatory Cells
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TIPE2 通过抑制 NF-κ B 信号传导和炎症细胞浸润来抑制铜绿假单胞菌角膜炎
DOI：
10.1093/infdis/jiz246
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发表时间：
2019-09-15
影响因子：
6.4
通讯作者：
Shi, Weiyun
中科院分区：
文献类型：
--
作者：
Wang, Qun;Ma, Li;Shi, Weiyun
背景探讨肿瘤坏死因子α（TNF-α）诱导蛋白8样2（TIPE 2）在铜绿假单胞菌（PA）角膜炎中的作用。使用八周龄TIPE 2敲除（TIPE 2（-/-））C57 BL/6小鼠及其野生型（WT）同窝出生小鼠。在感染后1、2和3天对角膜疾病进行分级，并在感染的角膜中进行裂隙灯、临床评分、组织病理学和免疫染色。收获角膜，检测TNF-α、白细胞介素-1 β（IL-1 β）和白细胞介素-6（IL-6）的信使核糖核酸（mRNA）水平。采用酶联免疫吸附试验（ELISA）检测各组蛋白水平，Western blot检测活化B细胞核因子κ轻链增强子（NF-κ B）信号分子的表达。使用体外人角膜上皮细胞（HCEC）来确定TIPE 2和TAK 1之间的关系。用TIPE 2短发夹状核糖核酸（shRNA）和脂多糖（LPS）处理HCECs，Western blot检测NF-κ B B信号分子的表达。铜绿假单胞菌感染诱导感染后2天小鼠角膜中TIPE 2表达降低。与对照组相比，TIPE 2缺陷小鼠对PA感染易感，并显示角膜炎症增加。NF-κ B信号转导和炎症细胞浸润的减少是TIPE 2介导的免疫调节所必需的。TIPE 2通过负调控TAK 1信号通路抑制角膜炎症反应，抑制炎症细胞浸润，从而增强宿主对PA感染的抵抗力。
Background. The role of tumor necrosis factor alpha (TNF-alpha) induced protein 8-like-2 (TIPE2) in Pseudomonas aeruginosa (PA) keratitis was explored.Methods. Eight-week-old TIPE2 knockout (TIPE2(-/-)) C57BL/6 mice and their wild-type (WT) littermates were used. Corneal disease was graded at 1, 2, and 3 days postinfection, and slit lamp, clinical score, histopathology, and immunostaining were performed in the infected corneas. The corneas were harvested, and messenger ribonucleic acid (mRNA) levels of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were tested. Enzyme-linked immunosorbent assay (ELISA) determined the protein levels, and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappa B) signaling molecules were tested by Western blot. In vitro human corneal epithelial cells (HCECs) were used to determine the relationship between TIPE2 and TAK1. The HCECs were treated with TIPE2 short hairpin ribonucleic acid (shRNA) and lipopolysaccharide (LPS) to test the NF-kappa B signaling molecules by Western blot.Results. Pseudomonas aeruginosa infection induced a decreased expression of TIPE2 in mouse corneas 2 days postinfection. Compared with the control group, TIPE2-deficient mice were susceptible to infection with PA and showed increased corneal inflammation. Reduced NF-kappa B signaling and inflammatory cell infiltration were required in the TIPE2-mediated immune modulation.Conclusions. TIPE2 promoted host resistance to PA infection by suppressing corneal inflammation via regulating TAK1 signaling negatively and inhibiting the infiltration of inflammatory cells.