RT Generic
T1 RNA sensors in human osteoarthritis and rheumatoid arthritis synovial fibroblasts: Immune regulation by vasoactive intestinal peptide
A1 Carrión Caballo, Mar
A1 Juarranz Moratilla, Yasmina
A1 Pérez García, Selene
A1 Jimeno, Rebeca
A1 Pablos Álvarez, José Luis
A1 Pérez Gomáriz, Rosa María
A1 Gutiérrez Cañas, Irene
AB Objective The aim of this study was to analyze both the constitutive and induced expression and function of double-stranded RNA (dsRNA; Toll-like receptor 3 [TLR-3], retinoic acid-inducible gene I [RIG-I], and melanoma differentiation-associated gene 5 [MDA5]) and single-stranded RNA (ssRNA; TLR-7) receptors in osteoarthritis (OA) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), by studying the transcription factors involved and the subsequent effects on antiviral interferon-β (IFNβ), the proinflammatory CXCL8 chemokine, and matrix metalloproteinase 3 (MMP-3). An additional goal was to study the effect of vasoactive intestinal peptide (VIP). Methods The expression of TLR-3, TLR-7, RIG-I, and MDA5 in cultured FLS was studied by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and Western blotting. Transcription factors were studied using the ELISA-based TransAM transcription factor kit. The expression of IFNβ, CXCL8 (interleukin-8), and MMP-3 was analyzed by RT-PCR and ELISA. Results FLS expressed TLR-3, TLR-7, RIG-I, and MDA5. The expression of TLR-3 and RIG-I was higher in RA FLS, while the expression of TLR-7 and MDA5 was higher in OA FLS. Stimulation with poly(I-C) induced the activation of IFN regulatory factor 3 (IRF-3), NF-κB, and activator protein 1 (AP-1) c-Jun as well as the subsequent production of IFNβ, CXCL8, and MMP-3. VIP reduced the activation of IRF-3 and the production of IFNβ in both OA and RA FLS. Imiquimod induced the activation of NF-κB, AP-1 c-Fos, and AP-1 c-Jun and the synthesis of CXCL8 and MMP-3. VIP significantly diminished MMP-3 production only in imiquimod-treated RA FLS. Conclusion The results of this study revealed a prominent function of FLS in the recognition of both dsRNA and ssRNA, which may be present in the joint microenvironment. This study also advances the healing function of the endogenous neuroimmune peptide VIP, which inhibited TLR-3-, RIG-I-, MDA5-, and TLR-7-mediated stimulation of antiviral, proinflammatory, and joint destruction mediators.
PB Wiley
SN 2326-5191
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/93685
UL https://hdl.handle.net/20.500.14352/93685
LA eng
NO Carrión, Mar, et al. «RNA Sensors in Human Osteoarthritis and Rheumatoid Arthritis Synovial Fibroblasts: Immune Regulation by Vasoactive Intestinal Peptide». Arthritis & Rheumatism, vol. 63, n.o 6, junio de 2011, pp. 1626-36. https://doi.org/10.1002/art.30294.
NO Supported by the Instituto de Salud Carlos III (grant PI080025 and RETICS Program grant RD08/0075, RIER) within VI PNDE I D I 2008/2011, by FEDER, and by Universidad Complutense de Madrid–Banco Santander Central Hispano (grant GR58/08)
NO Instituto de Salud Carlos III
NO European Commission
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 9 abr 2025