PMID- 35340587 OWN - NLM STAT- MEDLINE DCOM- 20220404 LR - 20220405 IS - 2314-7156 (Electronic) IS - 2314-8861 (Print) IS - 2314-7156 (Linking) VI - 2022 DP - 2022 TI - Ebosin Attenuates the Inflammatory Responses Induced by TNF-alpha through Inhibiting NF-kappaB and MAPK Pathways in Rat Fibroblast-Like Synoviocytes. PG - 9166370 LID - 10.1155/2022/9166370 [doi] LID - 9166370 AB - Tumor necrosis factor-alpha (TNF-alpha) lies at the apex of signal transduction cascades that results in induced destruction of joints in rheumatoid arthritis. It is therefore of great medicinal interest to modulate the cellular responses to TNF-alpha. Ebosin, a novel exopolysaccharide derived from Streptomyces sp, has been demonstrated to have remarkable therapeutic actions on collagen-induced arthritis in rats, while it also suppressed the production of IL-1beta, TNF-alpha, and IL-6 at both mRNA and protein levels in cultured fibroblast-like synoviocytes. In order to further understand the potential mechanisms involved in the anti-inflammatory effects of ebosin at molecular level, we investigated the impact of it on the activation of MAPK and NF-kappaB pathways following TNF-alpha induced in fibroblast-like synoviocytes (FLS). The results showed that the phosphorylation levels of TNF-alpha-induced p38, JNK1, JNK2, IKKalpha, IKKbeta, and IkappaB, as well as NF-kappaB nuclear translocation, were reduced significantly in FLS cells in response to ebosin. Furthermore, we proved that ebosin decreased the level of NF-kappaB in the nucleus and blocked the DNA-binding ability of NF-kappaB using electrophoresis mobility gel shift assay. Besides, low levels of matrix metalloproteinases (MMP-1 and MMP-3) and chemokines (interleukin-8 and RANTES) were found in TNF-alpha-stimulated fibroblast-like synoviocytes treated with ebosin. These results indicate that ebosin can suppress a range of activities in both MAPK and NF-kappaB pathways induced by TNF-alpha in rat fibroblast-like synoviocytes, which provides a rationale for examining the use of ebosin as a potential therapeutic candidate for rheumatic arthritis. CI - Copyright (c) 2022 Yang Zhang et al. FAU - Zhang, Yang AU - Zhang Y AUID- ORCID: 0000-0001-7462-2935 AD - NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, 100050 Beijing, China. AD - Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. FAU - Wang, Lifei AU - Wang L AD - NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, 100050 Beijing, China. FAU - Bai, Liping AU - Bai L AD - NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, 100050 Beijing, China. FAU - Jiang, Rong AU - Jiang R AD - NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, 100050 Beijing, China. FAU - Wu, Jianbo AU - Wu J AD - NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, 100050 Beijing, China. FAU - Li, Yuan AU - Li Y AUID- ORCID: 0000-0001-7110-4622 AD - NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantan Xili, 100050 Beijing, China. LA - eng PT - Journal Article DEP - 20220317 PL - Egypt TA - J Immunol Res JT - Journal of immunology research JID - 101627166 RN - 0 (NF-kappa B) RN - 0 (Polysaccharides, Bacterial) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (ebosin) SB - IM MH - Animals MH - Fibroblasts MH - *NF-kappa B/metabolism MH - Polysaccharides, Bacterial MH - Rats MH - *Synoviocytes/metabolism MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC8947919 COIS- All authors declare no conflict of interest. EDAT- 2022/03/29 06:00 MHDA- 2022/04/05 06:00 PMCR- 2022/03/17 CRDT- 2022/03/28 05:11 PHST- 2021/07/06 00:00 [received] PHST- 2021/12/04 00:00 [revised] PHST- 2022/01/22 00:00 [accepted] PHST- 2022/03/28 05:11 [entrez] PHST- 2022/03/29 06:00 [pubmed] PHST- 2022/04/05 06:00 [medline] PHST- 2022/03/17 00:00 [pmc-release] AID - 10.1155/2022/9166370 [doi] PST - epublish SO - J Immunol Res. 2022 Mar 17;2022:9166370. doi: 10.1155/2022/9166370. eCollection 2022.