PMID- 21337319
OWN - NLM
STAT- MEDLINE
DCOM- 20110817
LR  - 20190828
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 63
IP  - 6
DP  - 2011 Jun
TI  - RNA sensors in human osteoarthritis and rheumatoid arthritis synovial 
      fibroblasts: immune regulation by vasoactive intestinal peptide.
PG  - 1626-36
LID - 10.1002/art.30294 [doi]
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-beta (IFNbeta), 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 IFNbeta, 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-kappaB, and activator protein 1 (AP-1) c-Jun as well 
      as the subsequent production of IFNbeta, CXCL8, and MMP-3. VIP reduced the 
      activation of IRF-3 and the production of IFNbeta in both OA and RA FLS. Imiquimod 
      induced the activation of NF-kappaB, 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.
CI  - Copyright (c) 2011 by the American College of Rheumatology.
FAU - Carrion, Mar
AU  - Carrion M
AD  - Departamento de Biologia Celular, Facultad de Biologia, Universidad Complutense 
      de Madrid, and Hospital 12 de Octubre, Madrid, Spain.
FAU - Juarranz, Yasmina
AU  - Juarranz Y
FAU - Perez-Garcia, Selene
AU  - Perez-Garcia S
FAU - Jimeno, Rebeca
AU  - Jimeno R
FAU - Pablos, Jose L
AU  - Pablos JL
FAU - Gomariz, Rosa P
AU  - Gomariz RP
FAU - Gutierrez-Canas, Irene
AU  - Gutierrez-Canas I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Aminoquinolines)
RN  - 0 (IRF3 protein, human)
RN  - 0 (Interferon Inducers)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Interleukin-8)
RN  - 0 (PLAAT4 protein, human)
RN  - 0 (RNA, Double-Stranded)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (TLR3 protein, human)
RN  - 0 (TLR7 protein, human)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (Transcription Factors)
RN  - 37221-79-7 (Vasoactive Intestinal Peptide)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.6.1.- (IFIH1 protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
RN  - EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1)
RN  - P1QW714R7M (Imiquimod)
SB  - IM
MH  - Aminoquinolines/pharmacology
MH  - Arthritis, Rheumatoid/*immunology
MH  - Cells, Cultured
MH  - DEAD-box RNA Helicases/biosynthesis
MH  - Fibroblasts/*immunology
MH  - Humans
MH  - Imiquimod
MH  - Interferon Inducers/pharmacology
MH  - Interferon Regulatory Factor-3/biosynthesis
MH  - Interferon-Induced Helicase, IFIH1
MH  - Interferon-beta/biosynthesis
MH  - Interleukin-8/biosynthesis
MH  - Matrix Metalloproteinase 3/biosynthesis
MH  - Osteoarthritis/*immunology
MH  - RNA, Double-Stranded/*immunology
MH  - Receptors, Retinoic Acid/biosynthesis
MH  - Synovial Fluid/*immunology
MH  - Toll-Like Receptor 3/biosynthesis
MH  - Toll-Like Receptor 7/biosynthesis
MH  - Transcription Factors/metabolism
MH  - Vasoactive Intestinal Peptide/*immunology
EDAT- 2011/02/22 06:00
MHDA- 2011/08/19 06:00
CRDT- 2011/02/22 06:00
PHST- 2011/02/22 06:00 [entrez]
PHST- 2011/02/22 06:00 [pubmed]
PHST- 2011/08/19 06:00 [medline]
AID - 10.1002/art.30294 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2011 Jun;63(6):1626-36. doi: 10.1002/art.30294.