DPP4 reduces proinflammatory cytokine production in human rheumatoid arthritis synovial fibroblasts

Chien Kuo Han, Wei Fang Lee, Chin Jung Hsu, Yuan Li Huang, Chih Yang Lin, Chun Hao Tsai, Chien Chung Huang, Yi Chin Fong, Min Huan Wu, Ju Fang Liu, Chih Hsin Tang

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by increasing levels of proinflammatory cytokines. The ubiquitous enzyme dipeptidyl peptidase-4 (DPP4, also known as CD26) regulates different immune disorders, although the effects of DPP4 in RA are uncertain. Here, we found lower levels of DPP4 in RA synovial tissues compared with normal tissues. DPP4 levels were also lower in a rat collagen-induced arthritis model than in control (healthy) rats. Overexpression of DPP4 or exogenous treatment of RA synovial fibroblasts with DPP4 reduced levels of proinflammatory interleukin (IL)-1β, IL-6, and IL-13, and increased anti-inflammatory IL-10 synthesis, while DPP4 inhibitors sitagliptin and vildagliptin increased proinflammatory cytokine production, indicating an enhanced risk of RA development. The evidence suggests that increasing DPP4 expression is a novel strategy for RA disease.

Original languageEnglish
Pages (from-to)8060-8069
Number of pages10
JournalJournal of Cellular Physiology
Issue number12
Publication statusPublished - Dec 2021


  • cytokine
  • DPP4
  • rheumatoid arthritis
  • sitagliptin
  • vildagliptin

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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