PMID- 35189277 OWN - NLM STAT- MEDLINE DCOM- 20220315 LR - 20220315 IS - 1096-1208 (Electronic) IS - 0882-4010 (Linking) VI - 164 DP - 2022 Mar TI - Endotoxin tolerance induced by Porphyromonas gingivalis lipopolysaccharide alters macrophage polarization. PG - 105448 LID - S0882-4010(22)00061-4 [pii] LID - 10.1016/j.micpath.2022.105448 [doi] AB - Endotoxin tolerance refers to a state refractory to subsequent lipopolysaccharide (LPS) stimulations following a primary LPS exposure. To study the relationship between endotoxin tolerance and macrophage polarization, endotoxin tolerance was induced by 1 mug/mL LPS from the periodontal pathogen, Porphyromonas gingivalis (P. gingivalis), in peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs). Repeated P. gingivalis LPS challenges increased the quantities of CD206+ PMs, while the number of CD86+CD206+ PMs was reduced compared with the non-tolerant group (p < 0.05). However, there were no changes in BMDMs (p > 0.05). Down regulations of TNF-alpha, IL-12, nitric oxide and MMP-2 production, and upregulated IL-10, MMP-9 levels and arginase-1 activities occurred in tolerant PMs and BMDMs (p < 0.05). P. gingivalis LPS-tolerant PMs and BMDMs also enhanced scrape-wound healing abilities of 15p-1 cells (p < 0.05). Expressions of phospho-signal transducer and activator of transcription 6 (p-STAT6) and protein tyrosine phosphatase 1B (PTP1B) were increased, while p-MEK1/2 levels were downregulated in tolerant PMs and BMDMs (p < 0.05). IL-10 production in tolerant Stat6 knockdown RAW264.7 cells was lower than tolerant control cells (p < 0.05). P. gingivalis LPS-tolerant macrophages represented an intermediate state between M1/M2 polarization, which functioned as M2-like cells, and led to limited inflammatory responses and enhanced wound healing activities. The PTP1B-MEK1/2-STAT6 signaling pathway might be involved in the polarization of tolerant macrophages. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Gu, Jian-Yu AU - Gu JY AD - Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. FAU - Fu, Zi-Bo AU - Fu ZB AD - Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. FAU - Jia-Lu Chen AU - Jia-Lu Chen AD - Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. FAU - Liu, Yu-Jie AU - Liu YJ AD - Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. FAU - Cao, Xian-Zi AU - Cao XZ AD - Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. FAU - Sun, Ying AU - Sun Y AD - Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: ebolasun@njmu.edu.cn. LA - eng PT - Journal Article DEP - 20220218 PL - England TA - Microb Pathog JT - Microbial pathogenesis JID - 8606191 RN - 0 (Lipopolysaccharides) SB - IM MH - Endotoxin Tolerance MH - *Lipopolysaccharides/metabolism MH - Macrophage Activation MH - Macrophages/metabolism MH - *Porphyromonas gingivalis OTO - NOTNLM OT - Porphyromonas gingivalis OT - endotoxin tolerance OT - lipopolysaccharide OT - macrophage polarization EDAT- 2022/02/22 06:00 MHDA- 2022/03/16 06:00 CRDT- 2022/02/21 20:10 PHST- 2021/08/14 00:00 [received] PHST- 2022/01/10 00:00 [revised] PHST- 2022/02/14 00:00 [accepted] PHST- 2022/02/22 06:00 [pubmed] PHST- 2022/03/16 06:00 [medline] PHST- 2022/02/21 20:10 [entrez] AID - S0882-4010(22)00061-4 [pii] AID - 10.1016/j.micpath.2022.105448 [doi] PST - ppublish SO - Microb Pathog. 2022 Mar;164:105448. doi: 10.1016/j.micpath.2022.105448. Epub 2022 Feb 18.