A newly developed PLD1 inhibitor ameliorates rheumatoid arthritis by regulating pathogenic T and B cells and inhibiting osteoclast differentiation

Jin Sil Park, Seung Cheon Yang, Doona Song, Sung Min Kim, Jeong Won Choi, Hye Yeon Kang, Ha Yeon Jeong, Gyoonhee Han, Do Sik Min, Mi La Cho, Sung Hwan Park

Research output: Contribution to journalArticlepeer-review

Abstract

Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline, plays multiple roles in inflammation. We investigated the therapeutic effects of the newly developed PLD1 inhibitors A2998, A3000, and A3773 in vitro and in vivo rheumatoid arthritis (RA) model. A3373 reduced the levels of LPS-induced TNF-α, IL-6, and IgG in murine splenocytes in vitro. A3373 also decreased the levels of IFN-γ and IL-17 and the frequencies of Th1, Th17 cells and germinal-center B cells, in splenocytes in vitro. A3373 ameliorated the severity of collagen-induced arthritis (CIA) and suppressed infiltration of inflammatory cells into the joint tissues of mice with CIA compared with vehicle-treated mice. Moreover, A3373 prevented systemic bone demineralization in mice with CIA and suppressed osteoclast differentiation and the mRNA levels of osteoclastogenesis markers in vitro. These results suggest that A3373 has therapeutic potential for RA.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalImmunology Letters
Volume263
DOIs
Publication statusPublished - 2023 Nov

Bibliographical note

Publisher Copyright:
© 2023

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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