PMID- 37088470 OWN - NLM STAT- MEDLINE DCOM- 20230802 LR - 20230802 IS - 2055-5822 (Electronic) IS - 2055-5822 (Linking) VI - 10 IP - 4 DP - 2023 Aug TI - Rnf144b alleviates the inflammatory responses and cardiac dysfunction in sepsis. PG - 2338-2344 LID - 10.1002/ehf2.14383 [doi] AB - AIMS: Sepsis is an inflammatory disease with high mortality and morbidity. Inflammation plays an essential role in sepsis, and suppressing inflammation has been shown to ameliorate sepsis. Rnf144b is an ubiquitin E3 ligation with anti-inflammation activities. Its precise roles in sepsis remain unknown. Here, we explored the function of Rnf144b in sepsis. METHODS AND RESULTS: We generated conditional knockout mice with Rnf144b deficiency in the myeloid cells. We monitored the Rnf144b expression in peripheral blood mononuclear cells from healthy donor and patients with sepsis, and in lipopolysaccharides (LPS)-treated bone marrow-derived macrophages (BMDMs). The cytokine expression between wild-type BMDMs and Rnf144b-deficient BMDMs after LPS and CpG treatments was compared. The survival rate and cardiac function were monitored. The activation of TANK binding kinase 1 and nuclear factor kappa-B was examined by Western blot and real-time PCR. Up-regulated expression of Rnf144b was observed in peripheral blood mononuclear cells from patients with sepsis. LPS induced the expression of Rnf144b in BMDMs. Rnf144b-deficient BMDMs produced more inflammatory cytokines after LPS or CpG stimulation. Septic mice with Rnf144b deficiency in myeloid cells had higher mortality and exacerbated cardiac dysfunction. Rnf144b interacted with TANK binding kinase 1 and Rnf144b deficiency resulted in impaired activation of TBK1 but enhanced activation of nuclear factor kappa-B. CONCLUSIONS: Rnf144b prevents inflammatory responses and cardiac dysfunction in sepsis. CI - (c) 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. FAU - Guo, Rennan AU - Guo R AD - Department of Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang Uygur Autonomous Region, 830001, China. FAU - Wang, Jingjing AU - Wang J AD - Department of Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang Uygur Autonomous Region, 830001, China. FAU - Tang, Wen AU - Tang W AD - Department of Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang Uygur Autonomous Region, 830001, China. FAU - Xiao, Dong AU - Xiao D AD - Department of Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang Uygur Autonomous Region, 830001, China. LA - eng PT - Journal Article DEP - 20230423 PL - England TA - ESC Heart Fail JT - ESC heart failure JID - 101669191 RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - EC 2.3.2.27 (Rnf146 protein, mouse) SB - IM MH - Animals MH - Mice MH - Cytokines/metabolism MH - *Heart Diseases MH - Inflammation/metabolism MH - Leukocytes, Mononuclear/metabolism MH - Lipopolysaccharides/metabolism/pharmacology MH - Macrophages/metabolism MH - NF-kappa B/metabolism MH - *Sepsis/complications/metabolism PMC - PMC10375149 OTO - NOTNLM OT - Cardiac dysfunction OT - Inflammation OT - Rnf144b OT - Sepsis COIS- The authors declare that they have no conflict of interest. EDAT- 2023/04/24 00:41 MHDA- 2023/07/31 11:43 PMCR- 2023/04/23 CRDT- 2023/04/23 20:22 PHST- 2023/02/10 00:00 [revised] PHST- 2022/10/18 00:00 [received] PHST- 2023/04/02 00:00 [accepted] PHST- 2023/07/31 11:43 [medline] PHST- 2023/04/24 00:41 [pubmed] PHST- 2023/04/23 20:22 [entrez] PHST- 2023/04/23 00:00 [pmc-release] AID - EHF214383 [pii] AID - 10.1002/ehf2.14383 [doi] PST - ppublish SO - ESC Heart Fail. 2023 Aug;10(4):2338-2344. doi: 10.1002/ehf2.14383. Epub 2023 Apr 23.