Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts

✍ Scribed by Yasmina Juarranz; Irene Gutiérrez-Cañas; Begoña Santiago; Mar Carrión; José L. Pablos; Rosa P. Gomariz

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 328 KB
• Volume: 58
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.23403

✦ Synopsis

Abstract

Objective

Vasoactive intestinal peptide (VIP) has shown potent antiinflammatory effects in murine arthritis and ex vivo in human rheumatoid arthritis (RA) synovial cells. To investigate the potential endogenous participation of this system in the pathogenesis of RA, we analyzed the expression and regulation of VIP and its functional receptors in human fibroblast‐like synoviocytes (FLS) from patients with osteoarthritis (OA) and patients with RA.

Methods

The expression of VIP was studied by reverse transcription–polymerase chain reaction (RT‐PCR), enzyme immunoassay, and immunofluorescence in cultured FLS, and by immunohistochemical analysis in synovial tissue. The expression and function of the potential VIP receptors in FLS were studied by RT‐PCR, determination of intracellular cAMP production, cell membrane adenylate cyclase (AC) activity, and interleukin‐6, CCL2, and CXCL8 production in response to VIP or specific agonists and antagonists.

Results

VIP expression was detected in human FLS at the messenger RNA and protein levels, and it was significantly decreased in RA FLS compared with OA FLS. VIP receptor type 1 (VPAC~1~) was the dominant AC‐coupled receptor in OA FLS, in contrast with RA FLS, in which VPAC~2~ was dominant. Tumor necrosis factor α–treated OA FLS reproduced the VIP and VPAC receptor expression pattern of RA FLS. The antagonistic effects of VIP on FLS proinflammatory factor production were reproduced by VPAC~1~‐ and VPAC~2~‐specific agonists in OA FLS and RA FLS, respectively.

Conclusion

VIP expression is down‐regulated in RA and in tumor necrosis factor α–treated FLS, suggesting that down‐regulation of this endogenous antiinflammatory factor may contribute to the pathogenesis of RA. In RA FLS, VPAC~2~ mediates the antiinflammatory effects of VIP, suggesting that VPAC~2~ agonists may be an alternative to VIP as antiinflammatory agents.