Abstract：
Secretory leucoprotease inhibitor (SLPI) has multifaceted functions, including inhibition of protease activity, antimicrobial functions, and anti-inflammatory properties. In this study, we show that SLPI plays a role in controlling pulmonary Pseudomonas aeruginosa infection. Mice lacking SLPI were highly susceptible to P. aeruginosa infection, however there was no difference in bacterial burden. Utilising a model of P. aeruginosa LPS-induced lung inflammation, human recombinant SLPI (hrSLPI) administered intraperitoneally suppressed the recruitment of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and resulted in reduced BALF and serum levels of inflammatory cytokines and chemokines. This anti-inflammatory effect of hrSLPI was similarly demonstrated in a systemic inflammation model induced by intraperitoneal injection of LPS from various bacteria or lipoteichoic acid, highlighting the broad anti-inflammatory properties of hrSLPI. Moreover, in bone-marrow-derived macrophages, hrSLPI reduced LPS-induced phosphorylation of p-IkB-α, p-IKK-α/β, p-P38, demonstrating that the anti-inflammatory effect of hrSLPI was due to the inhibition of the NFκB and MAPK pathways. In conclusion, administration of hrSLPI attenuates excessive inflammatory responses and is therefore, a promising strategy to target inflammatory diseases such as acute respiratory distress syndrome or sepsis and could potentially be used to augment antibiotic treatment.
摘要：
分泌型白细胞蛋白酶抑制剂(SLPI)具有多方面的功能，包括抑制蛋白酶活性，抗菌功能，和抗炎特性。在这项研究中,我们表明SLPI在控制肺部铜绿假单胞菌感染中起作用。缺乏SLPI的小鼠对铜绿假单胞菌感染高度敏感，然而，细菌负荷没有差异。利用铜绿假单胞菌LPS诱导的肺部炎症模型，腹膜内给予人重组SLPI(hrSLPI)抑制支气管肺泡灌洗液(BALF)中炎性细胞的募集,并导致BALF和血清炎性细胞因子和趋化因子水平降低.hrSLPI的这种抗炎作用类似地在通过腹膜内注射来自各种细菌或脂磷壁酸的LPS诱导的全身性炎症模型中得到证实。突出hrSLPI的广泛抗炎特性。此外，在骨髓来源的巨噬细胞中，hrSLPI降低LPS诱导的p-IkB-α磷酸化，p-IKK-α/β,p-P38，证明hrSLPI的抗炎作用是由于NFκB和MAPK途径的抑制。总之,hrSLPI的给药减弱过度的炎症反应，因此，这是针对炎症性疾病如急性呼吸窘迫综合征或败血症的有希望的策略，可能用于增强抗生素治疗。
