The SMAC mimetic birinapant alleviates lipopolysaccharide-induced acute lung injury by inhibiting MAPK signaling

作者全名："Hu, Hui; Ma, Man; Li, Tao; Shi, Li; Li, Peizhi"

作者地址："[Hu, Hui; Ma, Man; Li, Tao; Shi, Li] Chongqing Univ, Chongqing Emergency Med Ctr, Dept Traumatol, Cent Hosp, 1 Jiankang Rd, Chongqing, Peoples R China; [Li, Peizhi] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China"

通信作者："Li, PZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China."

来源：IMMUNOLOGY LETTERS

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001113703600001

JCR分区：Q3

影响因子：3.3

年份：2023

卷号：264

期号：　

开始页：31

结束页：35

文献类型：Article; Early Access

关键词：Birinapant; Lipopolysaccharide; Acute lung injury; Macrophage

摘要："The second mitochondria-derived activator of caspases (SMAC) mimetic birinapant attenuated liver injury by inhibited the degradation of tumor necrosis factor receptor-associated factor 3 (TRAF3) and activation of mitogen-activated protein kinase (MAPK) signaling pathway in liver macrophage, but its role in LPS induced acute lung injury (ALI) is not understood. The present study was to investigate the effects of birinapant on ALI and its possible mechanism. A dose of birinapant (30 mg/kg) or a vehicle was administered intravenously 24 hours before LPS (100 mu g) stimulation in mice. The levels of TNF-alpha, IL-6 and IL-1 beta in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The infiltrated macrophages and expression of monocyte chemoattractant protein-1 (MCP-1) was determined by immunohistochemistry staining in the lung tissues. The JNK and p38 MAPK activation, protein expression and K48-linked polyubiquitination of TRAF3 were determined in alveolar macrophage cell line (MH-S cells) after 1 mu g/ml LPS stimulation. The results showed that the birinapant downregulated the levels of TNF-alpha, IL-6 and IL-1 beta in the BALF. In addition, birinapant markedly inhibited macrophages infiltration and MCP-1 protein expression in lung tissues. At last, birinapant suppressed the MAPKsignaling pathway and K48-linked ubiquitinated degradation of TRAF3 in MH-S cells after LPS administration. In conclusion, the results proved that birinapant protected against LPS-induced ALI through inhibiting MAPK activation and K48-linked ubiquitination of TRAF3 in alveolar macrophages."

基金机构：Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0135]; Chongqing Municipal Natural Science Foundation [cstc2020jcyj- msxmX0953]; Foundation of Chongqing Emergency Medical Center [JJZX201805]; Kuanren Talents Program of the Second Affliated Hospital of Chongqing Medical University

基金资助正文："The authors acknowledge the financial support for this project by the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0135) , Chongqing Municipal Natural Science Foundation (cstc2020jcyj- msxmX0953) , the Foundation of Chongqing Emergency Medical Center (JJZX201805) and Kuanren Talents Program of the Second Affliated Hospital of Chongqing Medical University."