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Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts

Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic...

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Autores principales: Inoue, Sho, Inahashi, Yuki, Itakura, Makoto, Inoue, Gen, Muneshige, Kyoko, Hirose, Tomoyasu, Iwatsuki, Masato, Takaso, Masashi, Miyagi, Masayuki, Uchida, Kentaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531480/
https://www.ncbi.nlm.nih.gov/pubmed/37762174
http://dx.doi.org/10.3390/ijms241813871
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author Inoue, Sho
Inahashi, Yuki
Itakura, Makoto
Inoue, Gen
Muneshige, Kyoko
Hirose, Tomoyasu
Iwatsuki, Masato
Takaso, Masashi
Miyagi, Masayuki
Uchida, Kentaro
author_facet Inoue, Sho
Inahashi, Yuki
Itakura, Makoto
Inoue, Gen
Muneshige, Kyoko
Hirose, Tomoyasu
Iwatsuki, Masato
Takaso, Masashi
Miyagi, Masayuki
Uchida, Kentaro
author_sort Inoue, Sho
collection PubMed
description Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.
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spelling pubmed-105314802023-09-28 Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts Inoue, Sho Inahashi, Yuki Itakura, Makoto Inoue, Gen Muneshige, Kyoko Hirose, Tomoyasu Iwatsuki, Masato Takaso, Masashi Miyagi, Masayuki Uchida, Kentaro Int J Mol Sci Article Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease. MDPI 2023-09-08 /pmc/articles/PMC10531480/ /pubmed/37762174 http://dx.doi.org/10.3390/ijms241813871 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Inoue, Sho
Inahashi, Yuki
Itakura, Makoto
Inoue, Gen
Muneshige, Kyoko
Hirose, Tomoyasu
Iwatsuki, Masato
Takaso, Masashi
Miyagi, Masayuki
Uchida, Kentaro
Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts
title Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts
title_full Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts
title_fullStr Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts
title_full_unstemmed Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts
title_short Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts
title_sort medermycin inhibits tnfα-promoted inflammatory reaction in human synovial fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531480/
https://www.ncbi.nlm.nih.gov/pubmed/37762174
http://dx.doi.org/10.3390/ijms241813871
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