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TLR5, a Novel and Unidentified Inflammatory Mediator in Rheumatoid Arthritis that Correlates with Disease Activity Score and Joint TNF-{alpha} Levels
The Journal of Immunology, 06/21/2012
Chamberlain ND et al. – The authors document the potential role of TLR5 ligation in modulating transcription of TNF–α from rheumatoid arthritis (RA) synovial fluid and the strong correlation of TLR5 and TNF–α with each other and with disease activity score in RA monocytes. The results suggest that expression of TLR5 may be a predictor for RA disease progression and that targeting TLR5 may suppress RA.
Methods- In this study, they show that TLR5 is elevated in RA and osteoarthritis ST lining and sublining macrophages and endothelial cells compared with normal individuals.
- Furthermore, expression of TLR5 is elevated in RA synovial fluid macrophages and RA peripheral blood monocytes compared with RA and normal peripheral blood in vitro–differentiated macrophages.
- They also found that TLR5 on RA monocytes is an important modulator of TNF–α in RA synovial fluid and that TLR5 expression on these cells strongly correlates with RA disease activity and TNF–α levels.
- Interestingly, TNF–α has a feedback regulation with TLR5 expression in RA monocytes, whereas expression of this receptor is regulated by IL–17 and IL–8 in RA macrophages and fibroblasts.
- They show that RA monocytes and macrophages are more responsive to TLR5 ligation compared with fibroblasts despite the proinflammatory response being mediated through the same signaling pathways in macrophages and fibroblasts.
