Analysis of the molecular mechanism by which extracellular acidification promotes LPA-induced inflammatory responses in rheumatoid arthritis synovial cells.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: Nochi Hiromi 徳島文理大学, 薬学部, 教授 (30183552)
• Co-Investigator(Kenkyū-buntansha): 伊藤 康一 徳島文理大学, 薬学部, 教授 (30291149)
• Research Collaborator: Tamoto Koichi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 関節リウマチ / 滑膜細胞 / プロトン感知性受容体 / リゾホスファチジン酸

Outline of Final Research Achievements

In RA, the proliferation of synovial cells is abnormally augmented and the pH of synovial fluid from RA patients is lower than that from healthy individuals. Therefore, we hypothesized that local acidification in the intra-articular cavity affects inflammatory responses.
The results revealed that an acidic extracellular pH induced COX-2 and ADAMTS-4 expressions through G protein-coupled pH-sensing receptor OGR1 in RA synovial cells from RA patients. Furthermore, the acidic extracellular pH synergistically enhanced LPA-induced COX-2 and ADAMTS-4 expressions.The results suggest that the acidification of synovial fluid is involved in exacerbation of the RA pathology by amplifying the inflammatory mediator-induced inflammatory response.

Free Research Field

細胞生物学