Department of Pharmacy, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.
FEMS Microbiol Lett. 2014 Jun;355(1):43-50. doi: 10.1111/1574-6968.12441. Epub 2014 Apr 28.
Although Pseudomonas aeruginosa is not typically susceptible to azithromycin (AZM) in in vitro tests, AZM improves the clinical outcome in patients with chronic respiratory infections, in which both the modulation of the host immune system and of bacterial virulence by AZM are thought to play an important role. However, there is currently little direct evidence showing the impact of bacteria pretreated with AZM on epithelial cells, which represents the first barrier to infecting P. aeruginosa. In this study, we pretreated P. aeruginosa with AZM and subsequently infected human bronchial epithelial cells (HBEs) in the absence of AZM. The results showed that AZM-pretreated P. aeruginosa (PAO1 and six different clinical isolates) significantly stimulated HBE cells to release IL-8, a crucial pro-inflammatory cytokine. This effect was not observed in a P. aeruginosa PAO1 mutant strain unable to produce the type III secretion system effector gene pcrV (strain PW4017). Our results suggest that AZM-pretreated P. aeruginosa could indirectly exacerbate pro-inflammation by inducing IL-8 production in HBEs.
虽然铜绿假单胞菌在体外试验中通常不易受阿奇霉素（AZM）的影响，但 AZM 可改善慢性呼吸道感染患者的临床转归，AZM 被认为在调节宿主免疫系统和细菌毒力方面发挥着重要作用。然而，目前直接证明 AZM 预处理细菌对代表铜绿假单胞菌感染第一道屏障的上皮细胞的影响的证据很少。在这项研究中，我们用 AZM 预处理铜绿假单胞菌，然后在没有 AZM 的情况下感染人支气管上皮细胞（HBE）。结果表明，AZM 预处理铜绿假单胞菌（PAO1 和六个不同的临床分离株）可显著刺激 HBE 细胞释放白细胞介素 8（IL-8），这是一种关键的促炎细胞因子。在无法产生 III 型分泌系统效应基因 pcrV（菌株 PW4017）的铜绿假单胞菌 PAO1 突变株中未观察到这种效应。我们的结果表明，AZM 预处理铜绿假单胞菌可能通过诱导 HBE 中白细胞介素 8 的产生，间接地加重炎症反应。
