PMID- 33839419 OWN - NLM STAT- MEDLINE DCOM- 20210720 LR - 20210720 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 556 DP - 2021 Jun 4 TI - TRIM37 negatively regulates inflammatory responses induced by virus infection via controlling TRAF6 ubiquitination. PG - 87-92 LID - S0006-291X(21)00558-1 [pii] LID - 10.1016/j.bbrc.2021.03.147 [doi] AB - Virus-induced cytokine storm has been a devastating actuality in clinic. The abnormal production of type I interferon (IFN-1) and upregulation of multiple cytokines induced strong inflammation and thus lead to shock and organ failure. As an E3 ubiquitin ligase, tripartite motif-containing 37 (TRIM37) regulates the ubiquitination of multiple proteins including TRAFs. RNA sequencing was performed to investigated the alteration of transcriptional profile of H1N1-infected patients. qRT-PCR assay was performed to investigate the RNA levels of certain genes. The group of immune cells was examined by the Flow cytometry analysis. H&E staining was applied to evaluate lung inflammation of WT and TRIM37-KO mice. ELISA assay was performed to demonstrate the alteration of multiple cytokines. The protein levels in NF-kB signaling was estimated by western blotting and immunoprecipitation assays were applied to demonstrate the direct interaction between TRIM37 and TRAF-6. The RNA level of TRIM37 decreased in CD11b(+) cells of Flu-infected patients. Knockout of TRIM37 inhibited the immune responses of H1N1-infected mice. TRIM37 deficiency reduced the levels of virous proinflammatory cytokines in bone marrow derived macrophages (BMDMs). Mechanically, TRIM37 promoted the K63-linked ubiquitination of TRAF6. TRIM37 negatively regulated inflammatory responses induced by virus infection via promoting TRAF6 ubiquitination at K63. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Zhao, Lifen AU - Zhao L AD - Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Taiyuan, 030032, Shanxi, China. FAU - Hao, Yanyan AU - Hao Y AD - Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Taiyuan, 030032, Shanxi, China. FAU - Song, Zhuohui AU - Song Z AD - Department of Physiology, Changzhi Medical College, No.161 Jiefang East Street, Changzhi, 046000, Shanxi, China. FAU - Fan, Yimin AU - Fan Y AD - Functional Comprehensive Laboratory, Changzhi Medical College, No.161 Jiefang East Street, Changzhi, 046000, Shanxi, China. FAU - Li, Shufen AU - Li S AD - Department of Physiology, Changzhi Medical College, No.161 Jiefang East Street, Changzhi, 046000, Shanxi, China. Electronic address: lsfddcy@163.com. LA - eng PT - Journal Article DEP - 20210408 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Inflammation Mediators) RN - 0 (TNF Receptor-Associated Factor 6) RN - 0 (Tripartite Motif Proteins) RN - EC 2.3.2.27 (TRIM37 protein, human) RN - EC 2.3.2.27 (TRIM37 protein, mouse) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Animals MH - Female MH - Humans MH - Inflammation/*metabolism MH - Inflammation Mediators/antagonists & inhibitors/immunology MH - Influenza A Virus, H1N1 Subtype/immunology MH - Influenza, Human/genetics/immunology/metabolism/virology MH - Mice MH - Mice, Inbred C57BL MH - Orthomyxoviridae Infections/genetics/immunology/*metabolism/*virology MH - TNF Receptor-Associated Factor 6/chemistry/*metabolism MH - Tripartite Motif Proteins/deficiency/genetics/*metabolism MH - Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism MH - *Ubiquitination OTO - NOTNLM OT - Interferon OT - Tripartite motif-containing 37 (TRIM37) OT - Ubiquitination OT - Viral infection COIS- Declaration of competing interest The authors declare that they have no conflict of interest. EDAT- 2021/04/12 06:00 MHDA- 2021/07/21 06:00 CRDT- 2021/04/11 20:35 PHST- 2021/03/24 00:00 [received] PHST- 2021/03/26 00:00 [accepted] PHST- 2021/04/12 06:00 [pubmed] PHST- 2021/07/21 06:00 [medline] PHST- 2021/04/11 20:35 [entrez] AID - S0006-291X(21)00558-1 [pii] AID - 10.1016/j.bbrc.2021.03.147 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2021 Jun 4;556:87-92. doi: 10.1016/j.bbrc.2021.03.147. Epub 2021 Apr 8.