Combination of LMT-28 and Metformin Improves Beneficial Anti-Inflammatory Effect in Collagen-Induced Arthritis
DC Field | Value | Language |
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dc.contributor.author | Park, Yeon-Hwa | - |
dc.contributor.author | Jang, You-Jin | - |
dc.contributor.author | Choi, Yongseok | - |
dc.contributor.author | Lee, Kyeong | - |
dc.contributor.author | Kim, Hee Jung | - |
dc.contributor.author | Cho, Okki | - |
dc.contributor.author | Lee, Hae-Ri | - |
dc.contributor.author | Heo, Tae-Hwe | - |
dc.date.accessioned | 2021-08-30T03:31:02Z | - |
dc.date.available | 2021-08-30T03:31:02Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2021-02 | - |
dc.identifier.issn | 0031-7012 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/49685 | - |
dc.description.abstract | Objectives: The interleukin-6 (IL-6)-mediated signaling pathway plays an essential role in the development of rheumatoid arthritis. LMT-28 suppresses the activation of the IL-6-mediated signaling by direct targeting of gp130. Although LMT-28 and metformin both possess anti-inflammatory activity, the beneficial effect of LMT-28 and metformin combination on a collagen-induced arthritis (CIA) model has not yet been investigated. This study aimed to investigate the anti-inflammatory effect and mechanism of a combination of LMT-28 and metformin in a CIA model. Methods: In MH7A cells, cell proliferation and the IL-6-mediated signaling pathway following administration of LMT-28 and metformin combination was analyzed through MTT assay and Western blotting. The level of T helper 17 (Th17) cell differentiation from CD4(+) T cells was analyzed in mouse splenocytes and human peripheral blood mononuclear cells. Arthritis score, incidence rate, inflammatory cytokine, and T-cell subsets were measured in CIA mice following administration of LMT-28 and metformin combination. Results: Combination treatment with LMT-28 and metformin diminished proliferation of MH7A cells and IL-6-mediated gp130, STAT3, and ERK signaling more than in individual treatments. Furthermore, the differentiation of CD4(+) T cells into Th17 cells was attenuated more by combination treatment with LMT-28 and metformin than individual treatments. The combination of LMT-28 and metformin ameliorated the arthritic score better than individual treatments. The combination significantly reduced tumor necrosis factor and IL-6 levels in the sera and had an anti-inflammatory effect on the distribution of Treg/Th17 cells in the lymph nodes. Conclusion: Combination treatment with LMT-28 and metformin significantly ameliorates arthritic symptoms in CIA by suppressing Th17 differentiation and IL-6 signaling. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | KARGER | - |
dc.title | Combination of LMT-28 and Metformin Improves Beneficial Anti-Inflammatory Effect in Collagen-Induced Arthritis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Yongseok | - |
dc.identifier.doi | 10.1159/000507451 | - |
dc.identifier.scopusid | 2-s2.0-85089729864 | - |
dc.identifier.wosid | 000617022800008 | - |
dc.identifier.bibliographicCitation | PHARMACOLOGY, v.106, no.1-2, pp.53 - 59 | - |
dc.relation.isPartOf | PHARMACOLOGY | - |
dc.citation.title | PHARMACOLOGY | - |
dc.citation.volume | 106 | - |
dc.citation.number | 1-2 | - |
dc.citation.startPage | 53 | - |
dc.citation.endPage | 59 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordAuthor | LMT-28 | - |
dc.subject.keywordAuthor | Metformin | - |
dc.subject.keywordAuthor | Collagen-induced arthritis | - |
dc.subject.keywordAuthor | T helper 17 | - |
dc.subject.keywordAuthor | Fibroblast-like synoviocytes | - |
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