Rheumatology Advance Access published online on November 30, 2005
Rheumatology, doi:10.1093/rheumatology/kei219
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1 Servicio de Reumatología, Hospital 12 de Octubre, Madrid, Spain
* To whom correspondence should be addressed. Objectives. Vasoactive intestinal peptide (VIP) has demonstrated therapeutic effects in arthritis by inhibiting both innate and acquired immune responses. We investigated the potential effects of VIP in the regulation of Toll-like receptor (TLR) expression and function in synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. Cultured fibroblast-like synoviocytes (FLS) were obtained from patients with RA and OA. The effects of VIP on basal or TNF- Results. TLR2, TLR4 and MyD88 mRNA expression was increased in RA FLS compared with OA FLS. The largest increase was observed for TLR4 and there was also overexpression at the protein level in RA FLS. TLR4 and MyD88 mRNA and proteins were induced by LPS and TNF- Conclusions. We demonstrate that VIP down-regulates LPS and TNF-
Received July 6, 2005
Accepted October 25, 2005
Original Papers
VIP down-regulates TLR4 expression and TLR4-mediated chemokine production in human rheumatoid synovial fibroblasts
I. Gutiérrez-Cañas 1,
Y. Juarranz 2,
B. Santiago 1,
A. Arranz 2,
C. Martinez 3,
M. Galindo 1,
M. Payá 1,
R. P. Gomariz 2,
and
J. L. Pablos 1 *
2 Departamento de Biología Celular, Facultad de Biología, Madrid, Spain
3 Departamento de Biología Celular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
J. L. Pablos, E-mail: jlpablos{at}h12o.es
Abstract 
or lipopolysaccharide (LPS)-induced TLR2, TLR4 and MyD88 expression and its effects on TLR4-mediated CCL2 and CXCL8 chemokine production were studied by reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. in RA FLS. VIP down-regulated the induced but not the constitutive expression of TLR4 and MyD88 in RA FLS. VIP treatment decreased CCL2 and CXCL8 chemokine production in response to TLR4 activation with LPS in RA FLS. activation of TLR4 expression and the TLR4 functional response in terms of proinflammatory chemokine production. These studies suggest that the pleiotropic anti-inflammatory actions of VIP involve inhibitory effects on TLR4 expression and signalling.
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