PMID- 31676250 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1879-1409 (Electronic) IS - 0305-4179 (Linking) VI - 46 IP - 3 DP - 2020 May TI - Tim4 regulates NALP3 inflammasome expression and activity during monocyte/macrophage dysfunction in septic shock patients. PG - 652-662 LID - S0305-4179(19)30267-0 [pii] LID - 10.1016/j.burns.2019.08.016 [doi] AB - Sepsis is the leading cause of death in burn patients. Monocytes/macrophages rapidly exhibit impaired production of proinflammatory cytokines and an elevated generation of anti-inflammatory cytokines in septic patients with immunosuppression. However, the expression patterns of Tim4 and Nod-like receptor protein 3 (NALP3) inflammasome and their roles during immunosuppression in septic shock patients are not well understood. Tim4 and NALP3 inflammasome expression in monocytes were downregulated in immunosuppressive patients with sepsis compared with healthy volunteers. Meanwhile, NALP3 inflammasome expression was upregulated by Tim4 overexpression in murine bone marrow-derived macrophages (BMDMs) and J774A.1 macrophages. Tim4 overexpression improved the ability of BMDMs and J774A.1 macrophages to produce proinflammatory cytokines and increased the expression of cleaved-caspase-1 (p10) after LPS/ATP stimulation. In addition, overexpression of Tim4 enhanced phagocytosis of apoptotic polymorphonuclear neutrophils (PMNs) by BMDMs and J774A.1 macrophages, while depletion of NALP3 in Tim4 overexpressing BMDMs and J774A.1 macrophages decreased phagocytosis of apoptotic PMNs. In summary, the expression of Tim4 and NALP3 inflammasome in monocytes/macrophages was downregulated in septic shock patients, and diminished expression of Tim4 and NALP3 inflammasome in monocytes/macrophages might play a critical role in sepsis-elicited immunosuppression. CI - Copyright (c) 2019 Elsevier Ltd and ISBI. All rights reserved. FAU - Liu, Zheng AU - Liu Z AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. FAU - Tan, Kezhe AU - Tan K AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. FAU - Bu, Lan AU - Bu L AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. FAU - Bo, Lulong AU - Bo L AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. FAU - Ni, Wen AU - Ni W AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. FAU - Fei, Miaomiao AU - Fei M AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. FAU - Chen, Fang AU - Chen F AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. FAU - Deng, Xiaoming AU - Deng X AD - Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China. Electronic address: deng_x@yahoo.com. FAU - Li, Jinbao AU - Li J AD - Department of Anesthesiology, Shanghai First People's Hospital, Jiaotong University, 200081, Shanghai, China. Electronic address: lijinbaoshanghai@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191030 PL - Netherlands TA - Burns JT - Burns : journal of the International Society for Burn Injuries JID - 8913178 RN - 0 (Cytokines) RN - 0 (Inflammasomes) RN - 0 (Membrane Proteins) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLRP3 protein, human) RN - 0 (Nlrp3 protein, mouse) RN - 0 (TIM-4 protein, mouse) RN - 0 (TIMD4 protein, human) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Adult MH - Animals MH - Apoptosis MH - Burns/immunology/metabolism MH - Case-Control Studies MH - Caspase 1/metabolism MH - Cytokines/metabolism MH - Down-Regulation MH - Female MH - Humans MH - Immunocompromised Host/*immunology MH - Inflammasomes/immunology MH - Inflammation MH - Macrophages/*immunology/metabolism MH - Male MH - Membrane Proteins/*immunology/metabolism MH - Mice MH - Middle Aged MH - Monocytes/*immunology/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/*immunology/metabolism MH - Neutrophils/immunology MH - Phagocytosis/immunology MH - Shock, Septic/*immunology/metabolism MH - Up-Regulation OTO - NOTNLM OT - Burn patients OT - NALP3 inflammasome OT - Sepsis OT - Tim4 EDAT- 2019/11/05 06:00 MHDA- 2021/06/22 06:00 CRDT- 2019/11/03 06:00 PHST- 2019/04/20 00:00 [received] PHST- 2019/08/28 00:00 [revised] PHST- 2019/08/29 00:00 [accepted] PHST- 2019/11/05 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2019/11/03 06:00 [entrez] AID - S0305-4179(19)30267-0 [pii] AID - 10.1016/j.burns.2019.08.016 [doi] PST - ppublish SO - Burns. 2020 May;46(3):652-662. doi: 10.1016/j.burns.2019.08.016. Epub 2019 Oct 30.