PT  - JOURNAL ARTICLE
AU  - Mieke F Roelofs
AU  - Mark H Wenink
AU  - Erik J M Toonen
AU  - Marieke J H Coenen
AU  - Leo A B Joosten
AU  - Wim B van den Berg
AU  - Piet L C M van Riel
AU  - Timothy R D J Radstake
TI  - The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis.
DP  - 2008 Apr 01
TA  - The Journal of Rheumatology
PG  - 558--561
VI  - 35
IP  - 4
4099  - http://www.jrheum.org/content/35/4/558.short
4100  - http://www.jrheum.org/content/35/4/558.full
SO  - J Rheumatol2008 Apr 01; 35
AB  - 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 B8 (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.