Tissue injury causes the secretion of stress hormone catecholamine and increases susceptibility to opportunistic infection. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that is a leading cause of microbial keratitis usually associated with ocular injury or contact lens wear. However, the effect of catecholamine on P. aeruginosa induced corneal infection is unknown. Here, we test if norepinephrine (NE) would promote the progression of P. aeruginosa keratitis in mice. Adult C57BL/6 mouse corneas were scarified and then inoculated with P. aeruginosa. The content of NE was elevated in corneas after scarification and inoculation with P. aeruginosa. Then, exogenous NE was applied to the infected corneas at 24 h after inoculation; control eyes were treated with sterile saline. Topical application of NE aggravated the severity of P. aeruginosa keratitis, accompanied with the increase of clinical score, bacterial load, pathological changes, neutrophils infiltration, bacterial virulence factors and proinflammatory factors levels. In order to further verify the role of NE, N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a neurotoxin selected to deplete NE, was injected subconjunctivally 12 h before scarification. Pre-depletion of local NE by DSP-4 significantly alleviated the severity of corneal infection. Moreover, NE was also confirmed to increase the bacterial growth and the expression of virulence factors gene in vitro. Together, these data showed that increased corneal NE content facilitated the progression of P. aeruginosa keratitis in mice by amplifying host excessive inflammatory response and bacterial virulence. Therefore, targeting NE may provide a potential strategy for the treatment of P. aeruginosa keratitis.

中文翻译：

---

角膜上皮损伤诱导的去甲肾上腺素可促进铜绿假单胞菌角膜炎。

组织损伤导致应激激素儿茶酚胺的分泌并增加了对机会性感染的敏感性。铜绿假单胞菌（P.aeruginosa）是一种机会病原体，是导致细菌性角膜炎的主要原因，通常与眼外伤或隐形眼镜配戴有关。但是，儿茶酚胺对铜绿假单胞菌诱导的角膜感染的作用尚不清楚。在这里，我们测试去甲肾上腺素（NE）是否会促进小鼠铜绿假单胞菌角膜炎的进展。将成年C57BL / 6小鼠角膜擦伤，然后接种铜绿假单胞菌。划痕和接种铜绿假单胞菌后，角膜中的NE含量升高。然后，在接种后24小时将外源性NE应用于感染的角膜。对照眼用无菌盐水治疗。NE的局部应用加剧了P的严重性。绿脓杆菌性角膜炎，伴有临床评分，细菌负荷，病理变化，中性粒细胞浸润，细菌毒力因子和促炎因子水平的升高。为了进一步验证NE的作用，N-（2-氯乙基）-N-乙基-2-溴苄胺盐酸盐（DSP-4）是一种选择消耗NE的神经毒素，在结石前12小时进行结膜下注射。通过DSP-4预先耗尽局部NE可显着减轻角膜感染的严重程度。此外，还证实NE在体外能增加细菌生长和致病因子基因的表达。总之，这些数据表明，通过增加宿主过度的炎症反应和细菌毒性，增加的角膜NE含量促进了小鼠铜绿假单胞菌角膜炎的发展。因此，