Department of Biotechnology and Bioinformatics, Korea University, Sejong, 30019, Republic of Korea.
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, Nankai University, Tianjin, 300071, China.
Microbes Infect. 2020 Nov-Dec;22(10):558-566. doi: 10.1016/j.micinf.2020.08.005. Epub 2020 Sep 5.
Pulmonary infection activates acute inflammatory responses by recruiting neutrophils to the infection site; this recruitment is promoted by interleukin-8 (IL-8). However, IL-8 production in response to Pseudomonas aeruginosa HtpG (PA1596), a homolog of heat shock protein 90, has yet not been characterized in detail. htpG expression in P. aeruginosa strain was elevated upon infection of host cells, and HtpG was released into bacterial culture supernatant. Treatment of dTHP-1 macrophages with recombinant HtpG (rHtpG) increased production of IL-8 in a dose- and time-dependent manner, and this effect was abolished by inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) p38 signaling. By contrast, the rHtpG-mediated production of IL-8 was increased by suppression of cylindromatosis (CYLD), suggesting that CYLD is a negative regulator of this pathway. The upregulation of expression was coordinated by signals transmitting through toll-like receptor 4 (TLR4) with the aid of CD91. Together, these observations suggest that P. aeruginosa HtpG activates NF-κB, CYLD, and p38 MAPK in a TLR4-and CD91-dependent manner, leading to stimulation of IL-8 production in macrophages.
肺部感染通过将中性粒细胞募集到感染部位来激活急性炎症反应；这种募集是由白细胞介素-8（IL-8）促进的。然而，铜绿假单胞菌 HtpG（PA1596），即热休克蛋白 90 的同源物，对其诱导产生白细胞介素-8的反应尚未得到详细描述。宿主细胞感染时，铜绿假单胞菌株中的 htpG 表达水平升高，HtpG 被释放到细菌培养上清液中。用重组 HtpG（rHtpG）处理 dTHP-1 巨噬细胞，会以剂量和时间依赖的方式增加白细胞介素-8 的产生，而核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）p38 信号的抑制则会消除这种效应。相比之下，rHtpG 介导的白细胞介素-8 的产生会被 cylindromatosis（CYLD）的抑制所增加，这表明 CYLD 是该通路的负调控因子。表达的上调是通过 Toll 样受体 4（TLR4）传递的信号与 CD91 协同作用来协调的。综上所述，这些观察结果表明，铜绿假单胞菌 HtpG 通过 TLR4 和 CD91 依赖性方式激活 NF-κB、CYLD 和 p38 MAPK，导致巨噬细胞中白细胞介素-8 的产生受到刺激。
