The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis
Roelofs, M.F.; Wenink, M.H.; Toonen, E.J.M.; Coenen, M.J.H.; Joosten, L.A.B.; van den Berg, W.B.; van Riel, P.L.C.M.; Radstake, T.R.D.J.
Journal of Rheumatology 35(4): 558-561
2008
ISSN/ISBN: 0315-162X PMID: 18381796 Document Number: 620808
Objective. To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA).Methods. Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein 138 (HSPB8). Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression.Results. TLR4 expression was similar in patients carrying or not carrying the variant. In contrast, both LPS and HSPB8 resulted in significantly lower secretion of IL-6, TNF-alpha, and IL-10 in those who carried the variant, whereas the frequency of CD14+ cells was higher in these individuals.Conclusion. TLR4 variant clearly reduces its potency to mediate signaling. Correction for CD14+ cells is necessary in comparable experiments.