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AB0055 Rho a protein and erk/jnk pathways regulate il-23 production by tlr2 in synovial macrophages from patients with rheumatoid arthritis
  1. S. Y. Park1,
  2. H. Y. Kim1,
  3. H. R. Lee1,
  4. S. H. Baek2,
  5. C. D. Kim1
  1. 1PUSAN NATIONAL UNIVERSITY, Yangsan-si, Gyeongsangnam-do
  2. 2Internal Medicine, Ilsin Christian Hospital, Pusan, Korea, Republic Of

Abstract

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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  3. Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 2003, 198:1951-1957.

  4. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005, 201: 233-240.

Disclosure of Interest None Declared

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