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。这种募集由白介素8（IL-8）促进。然而，尚未详细描述响应于铜绿假单胞菌HtpG（PA1596）（热休克蛋白90的同源物）的IL-8产生。htpG在铜绿假单胞菌中的表达当宿主细胞感染时，该菌株升高，并且HtpG释放到细菌培养物上清液中。用重组HtpG（rHtpG）处理dTHP-1巨噬细胞以剂量和时间依赖性方式增加IL-8的产生，并且通过抑制核因子-κB（NF-κB）和促分裂原活化蛋白而消除了该作用。激酶（MAPK）p38信号传导。相比之下，rHtpG介导的IL-8的产生通过抑制圆柱体病（CYLD）得以增加，表明CYLD是该途径的负调控因子。表达的上调与借助于CD91通过通行费样受体4（TLR4）传递的信号协调。在一起，这些观察结果表明铜绿假单胞菌 HtpG以TLR4和CD91依赖性方式激活NF-κB，CYLD和p38 MAPK，从而刺激巨噬细胞中IL-8的产生。