PMID- 21708001
OWN - NLM
STAT- MEDLINE
DCOM- 20120313
LR  - 20211020
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 13
IP  - 3
DP  - 2011 Jun 27
TI  - Arthritis is associated with T-cell-induced upregulation of Toll-like receptor 3 
      on synovial fibroblasts.
PG  - R103
LID - 10.1186/ar3384 [doi]
AB  - INTRODUCTION: Toll-like receptors (TLRs) are likely to play crucial roles in the 
      pathogenesis of rheumatoid arthritis (RA). The aim of this study was to determine 
      the key TLRs in synovium and explore their roles in the activation of 
      fibroblast-like synoviocytes (FLSs) mediated by T cells in arthritis. METHODS: 
      Pristane-induced arthritis (PIA) was established by subcutaneous injection with 
      pristane at the base of the rat's tail. TLR expression in synovium from PIA rats 
      was detected at different time points by performing real-time PCR. 
      Polyinosinic:polycytidylic acid (poly(I:C)) was intra-articularly administrated 
      to PIA rats, and arthritis was monitored macroscopically and microscopically. 
      Synovial TLR3 was detected by immunohistochemical staining. Rat FLSs were 
      stimulated with pristane-primed T cells or pristane-primed, T-cell conditioned 
      medium. The intervention of TLR3 in FLSs was achieved by specific short-hairpin 
      RNA (shRNA) or an antibody. The migration ability of FLSs was measured by using 
      the scratch test, and gene expression was detected by using real-time PCR. FLSs 
      from RA patients were stimulated with various cytokines and TLR ligands, and TLR3 
      expression was detected by performing real-time PCR. In addition, with different 
      concentrations of poly(I:C) stimulation, TLR3 expression of FLSs from RA patients 
      and patients with osteoarthritis (OA) was compared. RESULTS: Synovium TLR3 
      displayed early and persistent overexpression in PIA rats. TLR3 was expressed in 
      FLSs, and local treatment with poly(I:C) synergistically aggravated the 
      arthritis. Rat FLSs co-cultured with pristane-primed T cells showed strengthened 
      migration ability and significant upregulation of TLR3, IFN-beta, IL-6 and matrix 
      metalloproteinase 3 (MMP3) expression, which could also be induced by 
      pristane-primed, T-cell conditioned medium. The upregulation of cytokines and 
      MMPs was blocked by shRNA or TLR3 antibodies. In RA FLSs with cytokine or TLR 
      ligand stimulation, TLR3 expression exhibited remarkable upregulation. 
      Furthermore, RA FLSs showed higher reactivity than OA FLSs to poly(I:C). 
      CONCLUSIONS: TLR3 in the synovium of PIA rats was overexpressed, and activation 
      of the TLR3 signaling pathway could aggravate this arthritis. The induction of 
      TLR3 in FLSs resulted from T cell-derived inflammatory stimulation and could 
      further mediate FLS activation in arthritis. We conclude that TLR3 upregulation 
      of FLSs activated by T cells results in articular inflammation.
FAU - Zhu, Wenhua
AU  - Zhu W
AD  - Department of Genetics and Molecular Biology, Xi'an Jiaotong University School of 
      Medicine, Yanta West Road 76, Xi'an, Shaanxi 710061, People's Republic of China.
FAU - Meng, Liesu
AU  - Meng L
FAU - Jiang, Congshan
AU  - Jiang C
FAU - He, Xiaojing
AU  - He X
FAU - Hou, Weikun
AU  - Hou W
FAU - Xu, Peng
AU  - Xu P
FAU - Du, Heng
AU  - Du H
FAU - Holmdahl, Rikard
AU  - Holmdahl R
FAU - Lu, Shemin
AU  - Lu S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110627
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (TLR3 protein, human)
RN  - 0 (TLR3 protein, rat)
RN  - 0 (Terpenes)
RN  - 0 (Toll-Like Receptor 3)
RN  - 26HZV48DT1 (pristane)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/chemically induced/*immunology/metabolism
MH  - Arthritis, Rheumatoid/*immunology/metabolism
MH  - Cell Movement/immunology
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/pharmacology
MH  - Disease Models, Animal
MH  - Female
MH  - Fibroblasts/*immunology/metabolism
MH  - Gene Expression/immunology
MH  - Humans
MH  - Immunosuppressive Agents/toxicity
MH  - Male
MH  - Osteoarthritis/immunology/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Severity of Illness Index
MH  - Signal Transduction/immunology
MH  - Synovial Membrane/cytology/immunology/metabolism
MH  - T-Lymphocytes/cytology/*immunology/metabolism
MH  - Terpenes/toxicity
MH  - Toll-Like Receptor 3/genetics/*immunology/metabolism
MH  - Up-Regulation/immunology
PMC - PMC3218918
EDAT- 2011/06/29 06:00
MHDA- 2012/03/14 06:00
PMCR- 2011/06/27
CRDT- 2011/06/29 06:00
PHST- 2010/12/07 00:00 [received]
PHST- 2011/05/08 00:00 [revised]
PHST- 2011/06/27 00:00 [accepted]
PHST- 2011/06/29 06:00 [entrez]
PHST- 2011/06/29 06:00 [pubmed]
PHST- 2012/03/14 06:00 [medline]
PHST- 2011/06/27 00:00 [pmc-release]
AID - ar3384 [pii]
AID - 10.1186/ar3384 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2011 Jun 27;13(3):R103. doi: 10.1186/ar3384.