| RRC ID |
72435
|
| 著者 |
Konishi H, Kanou SE, Yukimatsu R, Inui M, Sato M, Yamamoto N, Nakano M, Koshiba M.
|
| タイトル |
Adenosine inhibits TNFα-induced MMP-3 production in MH7A rheumatoid arthritis synoviocytes via A2A receptor signaling.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Adenosine causes the anti-inflammatory effect of MTX; however, the contributions of synoviocyte adenosine receptors (AdoRs) are unknown, and matrix metalloproteinase 3 (MMP-3) is released by fibroblast-like synoviocytes in response to inflammatory signaling. To understand the mechanism of the clinical observation that the matrix proteinase-3 concentration of patients with rheumatoid arthritis treated successfully with methotrexate does not usually normalize, we investigated the effects of A2A AdoR activation and inhibition on tumor necrosis factor-alpha (TNFα)-induced MMP-3 release by MH7A human rheumatoid synovial cells. MH7A cells constitutively expressed membrane-associated A2A AdoRs, and HENECA enhanced intracellular cAMP. Stimulation with TNFα markedly enhanced release of MMP-3 from MH7A cells, whereas HENECA partially and dose-dependently inhibited TNFα-evoked MMP-3 release. Similarly, dbcAMP partially inhibited TNFα-induced MMP-3 release. Pretreatment with ZM241385 reversed the inhibitory effects of HENECA. Further, TNFα induced p38 MAPK and ATF-2 phosphorylation, whereas HENECA suppressed p38 MAPK and ATF-2 phosphorylation. We concluded that adenosine signaling via A2A AdoRs, adenylyl cyclase, and cAMP reduces TNFα-induced MMP-3 production by interfering with p38 MAPK/ATF-2 activity. Activation of A2A AdoR signaling alone using HENECA did not reduce TNFα-induced MMP-3 production to the basal levels, which may explain why MTX usually decreases but does not eliminate serum MMP-3.
|
| 巻・号 |
12(1)
|
| ページ |
6033
|
| 公開日 |
2022-4-11
|
| DOI |
10.1038/s41598-022-10012-6
|
| PII |
10.1038/s41598-022-10012-6
|
| PMID |
35410356
|
| PMC |
PMC9001689
|
| MeSH |
Adenosine / pharmacology
Arthritis, Rheumatoid* / pathology
Humans
Matrix Metalloproteinase 3 / metabolism*
Methotrexate / pharmacology
Methotrexate / therapeutic use
Receptor, Adenosine A2A / metabolism*
Synovial Membrane / pathology
Synoviocytes* / pathology
Tumor Necrosis Factor-alpha / pharmacology
Tumor Necrosis Factor-alpha / therapeutic use
p38 Mitogen-Activated Protein Kinases
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
MH7A(RCB1512) |
