Authors: Hong, K.-H.; Cho, M.-L.; Min, S.-Y.; Shin, Y.-J.; Yoo, S.-A.; Choi, J.-J.; Kim, W.-U.; Song, S.-W.; Cho, C.-S.

Source: Clinical & Experimental Immunology, Volume 147, Number 3, March 2007 , pp. 573-579(7)

Publisher: Wiley-Blackwell

Abstract:

Summary

Interleukin (IL)-4 has been demonstrated to have anti-inflammatory and anti-tumour activity. Because aberrant angiogenesis is a significant pathogenic component of tumour growth and chronic inflammation, we investigated the effect of IL-4 on the production of vascular endothelial growth factor (VEGF) by synovial fibroblasts derived from patients with rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) were prepared from synovial tissues of RA and incubated with different concentrations of IL-4 in the presence or absence of transforming growth factor (TGF)-β. VEGF level was measured by enzyme-linked immunosorbent assay and semiquantitative reverse transcription-polymerase chain reaction. Treatment of FLS with IL-4 alone caused a dose-dependent increase in VEGF levels. In contrast, IL-4 exhibited the inhibitory effect on VEGF production when FLS were stimulated with TGF-β. Combined treatment of IL-4 and IL-10 inhibited TGF-β-induced VEGF production in an additive fashion. TGF-β increased the induction of cyclooxygenase-2 mRNA, which was inhibited significantly by the treatment of IL-4. NS-398, a COX-2 inhibitor, inhibited TGF-β-induced VEGF production in a dose-dependent manner. Furthermore, exogenous addition of prostaglandin E₂ (PGE₂) restored IL-4 inhibition on TGF-β induced VEGF production. Collectively, our results suggest that IL-4 have an anti-angiogenic effect, especially in the inflammatory milieu of RA by inhibiting the VEGF production in synovial fibroblasts.

Keywords: angiogenesis; fibroblast-like synoviocyte; IL-4; rheumatoid arthritis; vascular endothelial growth factor

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2249.2006.03295.x

Affiliations: 1: Department of Orthopedic Surgery, St Mary's Hospital, Research Institute of Immunobiology, Catholic University of Korea, Seoul, Korea

Publication date: 2007-03-01

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• In this Subject: Microbiology ,  Allergy & Immunology
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