Background TLR2 expression upon application of TNF-a, IL-1b, and LPSin synovial fibroblasts from joints of RA patients (1, 2).IL-23 is involved in autoimmune diseases such as RA and psoriasis, in which the cellular mechanism of IL-23 is associated with self-reactive production of IL-17, IL-6, and TNF-a, thereby playing a critical role in development of autoimmune inflammation (3, 4).
Objectives This study aimed to elucidate the signaling pathways of TLR2-mediated IL-23 production in synovial fluid macrophages from patients with rheumatoid arthritis (RA).
Methods Expression of IL-23 was measured by ELISA and immunofluorescence in synovial fluid macrophages from RA patients. RhoA activity was assessed by pull-down assay. The role of MAP kinase was investigated using selective inhibitors and western blot.
Results TLR2 ligand LTA-stimulated IL-23 production measured by ELISAwas elevated time- and concentration-dependently. TLR2 stimulation by LTA significantly increased not only GTP-bound RhoA activity but also phosphorylation of ERK and JNK in RA macrophages in association with increased nuclear translocation and DNA-binding activity of NF-kB. Inhibition of RhoA by Y27632, and of ERK and JNK phosphorylation by PD98059 and SP600125, resulted in suppression of LTA-induced NF-kB activation and IL-23 production.
Conclusions TLR2-mediated IL-23 production in synovial fluid macrophages was mediated through activation of RhoA GTPase and phosphorylation of ERK/JNK in association with NF-kB activation.
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Disclosure of Interest None Declared