Overexpression of toll-like receptor 3 in spleen is associated with experimental arthritis in rats.
This study is to investigate the regulation of Toll-like receptor (TLR) expression in systemic immune reactions in different arthritis rat models, which will provide evidence to understand the mechanisms of rheumatoid arthritis further. Arthritis-susceptible DA rats were used to induce arthritis by pristane or collagen type II, and TLR2, 3, 4 and 7 expression levels in spleen were detected by real-time quantitative polymerase chain reaction. TLR3 mRNA expression in spleen of both collagen-induced arthritis and pristane-induced arthritis (PIA) rats was increased significantly at 26 and 70 days after arthritis induction. The overexpression of TLR3 was confirmed by Western blotting. Methotrexate was administrated peritoneally to PIA rats, and phytol was applied subcutaneously to PIA rats. Both methotrexate and phytol treatment could alleviate arthritis severity and block TLR3 induction. However, in arthritis-resistant E3 rats injected with pristane, TLR3 expression of spleen was unaltered. PIA in MHC congenic DA.1U rats had mild symptoms, whereas TLR3 mRNA expression in spleen of DA.1U rats showed an impaired induction at D26. So we conclude that overexpression of splenic TLR3 is strongly associated with arthritis in rats, which suggests that TLR3 should be a most vital TLR in spleen to regulate the initiation and development of experimental arthritis and may be as an intriguing therapeutic opportunity for human rheumatoid arthritis.
Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, China.
W
W
Zhu
L
L
Meng
C
C
Jiang
J
J
Xu
B
B
Wang
Y
Y
Han
S
S
Lu
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015153:Blotting, Western; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*; D015854:Up-Regulation
D018501:Antirheumatic Agents; C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3