PMID- 38049081 OWN - NLM STAT- MEDLINE DCOM- 20240110 LR - 20240119 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 434 IP - 2 DP - 2024 Jan 15 TI - Dual-specificity phosphatase 5-mediated fatty acid oxidation promotes Mycobacterium bovis BCG -induced inflammatory responses. PG - 113869 LID - S0014-4827(23)00420-2 [pii] LID - 10.1016/j.yexcr.2023.113869 [doi] AB - Mycobacterium tuberculosis (Mtb) reprograms FAs metabolism of macrophages during infection and affects inflammatory reaction eventually, however, the mechanism remains poorly understood. Here we show that Mycobacterium bovis (BCG) induces DUSP5 expression through TLR2-MAPKs signaling pathway and promotes fatty acid oxidation (FAO). Silencing DUSP5 by adeno-associated virus vector (AAV) ameliorates lung injury and DUSP5 knockdown reduces the expression of IL-1beta, IL-6 and inactivated NF-kappaB signaling in BCG-infected macrophages. Of note, DUSP5 specific siRNA increases the content of free fatty acids (FFAs) and triglyceride (TG), but represses the expression of FAO associated enzymes such as CPT1A and PPARalpha, suggesting DUSP5 mediated FAO during BCG infection. Moreover, Inhibiting FAO by pharmacological manner suppresses IL-1beta, IL-6, TNF-alpha expression and relieves lung damage. Taken together, our data indicates DUSP5 mediates FAO reprogramming and promotes inflammatory response to BCG infection. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Luo, Jia AU - Luo J AD - Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China; General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Tian, Zengjian AU - Tian Z AD - School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Song, Fuyang AU - Song F AD - College of Life Science, Ningxia University, Yinchuan, Ningxia, 750021, China. FAU - Ren, Chao AU - Ren C AD - General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Liu, Wenmiao AU - Liu W AD - General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China; The Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China. Electronic address: liuwenmiao@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231202 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Interleukin-6) RN - EC 3.1.3.48 (Dual-Specificity Phosphatases) RN - 0 (Fatty Acids) SB - IM MH - *Mycobacterium bovis MH - Interleukin-6/genetics/metabolism MH - Signal Transduction MH - Dual-Specificity Phosphatases/genetics MH - Fatty Acids OTO - NOTNLM OT - BCG OT - Dual specificity phosphatase 5 OT - Fatty acid oxidation OT - Inflammation OT - Macrophage COIS- Declaration of competing interest This work has not been submitted to any other journals and all the authors have contributed to the paper and have reviewed the manuscript and agree with its contents. EDAT- 2023/12/05 00:41 MHDA- 2024/01/10 06:42 CRDT- 2023/12/04 19:27 PHST- 2023/09/12 00:00 [received] PHST- 2023/11/24 00:00 [revised] PHST- 2023/11/28 00:00 [accepted] PHST- 2024/01/10 06:42 [medline] PHST- 2023/12/05 00:41 [pubmed] PHST- 2023/12/04 19:27 [entrez] AID - S0014-4827(23)00420-2 [pii] AID - 10.1016/j.yexcr.2023.113869 [doi] PST - ppublish SO - Exp Cell Res. 2024 Jan 15;434(2):113869. doi: 10.1016/j.yexcr.2023.113869. Epub 2023 Dec 2.