PMID- 33229071 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20210216 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 129 DP - 2021 Jan TI - HtrA2 is required for inflammatory responses in BMDMs via controlling TRAF2 stability in collagen-induced arthritis. PG - 78-85 LID - S0161-5890(20)30529-0 [pii] LID - 10.1016/j.molimm.2020.10.024 [doi] AB - Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by the destruction of cartilage and bone. The present study aims to investigate the role of HtrA serine peptidase 2 (HtrA2) in the collagen-induced arthritis. The expressions of HtrA2 were determined in the database BioGPS and bone marrow-derived macrophages (BMDMs). The populations of myeloid and lymphoid cells were determined in wild type and HtrA2 knockout (HtrA2(MKO)) mice using flow cytometry. In addition, the expressions of pro-inflammatory cytokines (Il6, Tnf, and Il1beta) were determined in the activated BMDMs from wild type (WT) and HtrA2(MKO) mice. STRING database was used to predict the interactive proteins of HtrA2 and Co-Immunoprecipitation was used to confirm these interactions. A collagen-induced arthritis model was established to investigate the effects of HtrA2 on the arthritis symptoms. It was found that HtrA2 reduction was associated with the activation of myeloid cells. Interestingly, HtrA2 deficiency did not affect the development of myeloid and lymphoid cells. Further studies demonstrated that HtrA2 deficiency suppressed the production of pro-inflammatory cytokines in BMDMs induced by lipopolysaccharide or CpG. Co-Immunoprecipitation results demonstrated that HtrA2 enhanced the stability of TNF receptor-associated factor 2 (TRAF2). HtrA2 participated in the activation of the inflammatory response in a collagen-induced arthritis model. In summary, HtrA2 modulates inflammatory responses in BMDMs by controlling TRAF2 stability in a collagen-induced arthritis mouse model. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Xu, Zhitong AU - Xu Z AD - Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China. FAU - Lin, Jinding AU - Lin J AD - Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China. FAU - Xie, Yongsong AU - Xie Y AD - Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China. FAU - Tang, Haifeng AU - Tang H AD - Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China. FAU - Xie, Junjie AU - Xie J AD - Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China. FAU - Zeng, Rongdong AU - Zeng R AD - Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China. Electronic address: zengrongdg@126.com. LA - eng PT - Journal Article DEP - 20201120 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Cytokines) RN - 0 (TNF Receptor-Associated Factor 2) RN - 0 (TRAF2 protein, mouse) RN - 9007-34-5 (Collagen) RN - EC 3.4.21.108 (High-Temperature Requirement A Serine Peptidase 2) RN - EC 3.4.21.108 (Htra2 protein, mouse) SB - IM MH - Animals MH - Arthritis, Experimental/chemically induced/metabolism MH - Arthritis, Rheumatoid/*chemically induced/*metabolism MH - Autoimmune Diseases/chemically induced/metabolism MH - Bone and Bones/metabolism MH - Cartilage/metabolism MH - Cells, Cultured MH - Collagen/*pharmacology MH - Cytokines/metabolism MH - Disease Models, Animal MH - High-Temperature Requirement A Serine Peptidase 2/*metabolism MH - Inflammation/*metabolism MH - Lymphocytes/metabolism MH - Macrophages/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Myeloid Cells/metabolism MH - TNF Receptor-Associated Factor 2/*metabolism OTO - NOTNLM OT - Arthritis OT - BMDMs OT - HtrA2 OT - Inflammation OT - TRAF2 EDAT- 2020/11/25 06:00 MHDA- 2021/02/17 06:00 CRDT- 2020/11/24 05:45 PHST- 2020/08/28 00:00 [received] PHST- 2020/09/29 00:00 [revised] PHST- 2020/10/27 00:00 [accepted] PHST- 2020/11/25 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2020/11/24 05:45 [entrez] AID - S0161-5890(20)30529-0 [pii] AID - 10.1016/j.molimm.2020.10.024 [doi] PST - ppublish SO - Mol Immunol. 2021 Jan;129:78-85. doi: 10.1016/j.molimm.2020.10.024. Epub 2020 Nov 20.