• Wuquan Li, Xiaochen Qiu, He Jiang, Yan Zhi, Jinfeng Fu, and Jun Liu.
• Burn Center of Yunnan Province, Second Affiliated Hospital of Kunming Medical University, Kunming, China.
• Int. Immunopharmacol. 2015 Dec 1; 29 (2): 560-567.

BackgroundUlinastatin (ULI), a serine protease inhibitor, had been widely used as a drug for patients with acute inflammatory disorders. However, evidence regarding the anti-inflammatory effect of ulinastatin was still lacking. In this study, we investigated the protective mechanisms of ULI in LPS-induced acute lung injury (ALI).MethodsALI was induced in mice by intratracheal instillation of LPS. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio and oxygenation index. The levels of inflammatory mediators, tumor necrosis factor-α, interleukin-1β, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by HE staining. The levels of NF-κB p65, AMPK, p-AMPK and IκBα expression were detected by Western blotting. Then, selective AMPK inhibitor Compound C was used to test whether AMPK activation was critical in protection process of ULI against LPS-induced ALI.ResultsUlinastatin pretreatment at doses of 15, 30 and 45mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and oxygenation index. Expression of IL-6, IL-1β, and TNF-α was suppressed by ULI at protein level in BALF. Additionally, the attenuation of inflammatory responses by ULI was closely associated with AMPK/NF-κB pathway and this effect was significantly inhibited by treatment with the AMPK inhibitor, Compound C.ConclusionsThe results presented here indicated that ULI has a protective effect against LPS-induced ALI and this effect may be attributed partly to decreased production of proinflammatory cytokines through the regulation of AMPK/NF-κB signaling pathway.Copyright © 2015 Elsevier B.V. All rights reserved.

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