CD40 engagement on synovial fibroblast up-regulates production of vascular endothelial growth factor

Chul Soo Cho, Mi La Cho, So Youn Min, Wan Uk Kim, Do June Min, Shin Seok Lee, Sung Hwan Park, Jongseon Choe, Ho Youn Kim

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


We tested the impact of CD40 engagement on the production of vascular endothelial growth factor (VEGF) from rheumatoid synovial fibroblasts. Fibroblast-like synovial cells (FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of CD40 ligand- transfected (CD40L+) L cells. VEGF levels were determined in the culture supernatants by ELISA. Stimulation of FLS by CD40L+ L cells increased the production of VEGF by 4.1-fold over the constitutive levels of unstimulated FLS. The CD40L on activated T cells from rheumatoid synovial fluid also up- regulated VEGF production from FLS. Neither indomethacin nor Abs to IL-1β, TNF-α, and TGF-β did affect CD40L-induced VEGF production. Stimulation of FLS with TNF-α, IL-β, and TGF-β increased VEGF production by 1.6-, 2.0-, and 5.2-fold, respectively, and displayed an additive effect on the production of VEGF by CD40L. VEGF mRNA expression was also up-regulated by the stimulation of FLS with membranes from the CD40L+ L cells. Dexamethasone completely abrogated CD40L-induced VEGF production. In addition, pyrrolidine dithiocarbamate partially down-regulated CD40L-induced VEGF production, showing that the NF-κ pathway was partly involved in the signaling of CD40L leading to VEGF production. Collectively, these results suggest that the interaction between CD40 on synovial fibroblasts and CD40L expressed on activated T lymphocytes may be directly involved in the neovascularization in rheumatoid synovitis by enhancing the production of VEGF.

Original languageEnglish (US)
Pages (from-to)5055-5061
Number of pages7
JournalJournal of Immunology
Issue number10
StatePublished - May 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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