PMID- 37913914 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20231216 IS - 1879-0542 (Electronic) IS - 0165-2478 (Linking) VI - 264 DP - 2023 Dec TI - The SMAC mimetic birinapant alleviates lipopolysaccharide-induced acute lung injury by inhibiting MAPK signaling. PG - 31-35 LID - S0165-2478(23)00180-3 [pii] LID - 10.1016/j.imlet.2023.10.008 [doi] AB - 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 mug) stimulation in mice. The levels of TNF-alpha, IL-6 and IL-1beta 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 1mug/ml LPS stimulation. The results showed that the birinapant down-regulated the levels of TNF-alpha, IL-6 and IL-1beta 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. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Hu, Hui AU - Hu H AD - Department of Traumatology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No.1 Jiankang Road, Yuzhong District, Chongqing, China. FAU - Ma, Man AU - Ma M AD - Department of Traumatology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No.1 Jiankang Road, Yuzhong District, Chongqing, China. FAU - Li, Tao AU - Li T AD - Department of Traumatology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No.1 Jiankang Road, Yuzhong District, Chongqing, China. FAU - Shi, Li AU - Shi L AD - Department of Traumatology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No.1 Jiankang Road, Yuzhong District, Chongqing, China. FAU - Li, Peizhi AU - Li P AD - Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: lipeizhi@cqmu.edu.cn. LA - eng PT - Journal Article DEP - 20231031 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - 0 (Lipopolysaccharides) RN - 6O4Z07B57R (birinapant) RN - 0 (TNF Receptor-Associated Factor 3) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.22.- (Caspases) RN - 0 (Interleukin-6) RN - 0 (Interleukin-1beta) SB - IM MH - Animals MH - Mice MH - *Mitogen-Activated Protein Kinases/metabolism MH - Lipopolysaccharides/pharmacology MH - TNF Receptor-Associated Factor 3/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Caspases/adverse effects/metabolism MH - Interleukin-6/metabolism MH - Signal Transduction MH - *Acute Lung Injury/chemically induced/drug therapy MH - Lung/pathology MH - Interleukin-1beta/metabolism MH - Mitochondria/metabolism OTO - NOTNLM OT - Acute lung injury OT - Birinapant OT - Lipopolysaccharide OT - Macrophage COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/11/02 00:42 MHDA- 2023/12/17 09:44 CRDT- 2023/11/01 20:28 PHST- 2023/05/17 00:00 [received] PHST- 2023/10/19 00:00 [revised] PHST- 2023/10/28 00:00 [accepted] PHST- 2023/12/17 09:44 [medline] PHST- 2023/11/02 00:42 [pubmed] PHST- 2023/11/01 20:28 [entrez] AID - S0165-2478(23)00180-3 [pii] AID - 10.1016/j.imlet.2023.10.008 [doi] PST - ppublish SO - Immunol Lett. 2023 Dec;264:31-35. doi: 10.1016/j.imlet.2023.10.008. Epub 2023 Oct 31.