Combination of LMT-28 and Metformin Improves Beneficial Anti-Inflammatory Effect in Collagen-Induced Arthritis
- Authors
- Park, Yeon-Hwa; Jang, You-Jin; Choi, Yongseok; Lee, Kyeong; Kim, Hee Jung; Cho, Okki; Lee, Hae-Ri; Heo, Tae-Hwe
- Issue Date
- 2월-2021
- Publisher
- KARGER
- Keywords
- LMT-28; Metformin; Collagen-induced arthritis; T helper 17; Fibroblast-like synoviocytes
- Citation
- PHARMACOLOGY, v.106, no.1-2, pp.53 - 59
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHARMACOLOGY
- Volume
- 106
- Number
- 1-2
- Start Page
- 53
- End Page
- 59
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/49685
- DOI
- 10.1159/000507451
- ISSN
- 0031-7012
- 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.
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Collections - College of Life Sciences and Biotechnology > Division of Biotechnology > 1. Journal Articles
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