Formato Vancouver:
Carrión M, Pérez-García S, Jimeno R, Juarranz Y, González-Álvaro I, Pablos JL et al. Inflammatory mediators alter interleukin-17 receptor, interleukin-12 and -23 expression in human osteoarthritic and rheumatoid arthritis synovial fibroblasts: immunomodulation by vasoactive intestinal Peptide. Neuroimmunomodulation. 2013;20(5):274-84.

PMID: 23880957

Contiene 49 referencias

Aims: To assess the contribution of fibroblast-like synoviocytes (FLS) to the inflammatory joint microenvironment under different pathogenic stimuli and their potential to respond to interleukin (IL)-17 and to determine whether the neuroimmunomodulatory vasoactive intestinal peptide (VIP) is able to modulate IL-17 receptor (IL-17R) and related cytokines. Methods: The effect of proinflammatory cytokines [tumor necrosis factor alpha (TNF alpha) and IL-17] and Toll-like receptor (TLR) ligands [poly(I: C) and lipopolysaccharide (LPS)] on IL-17R expression and IL-12 and IL-23 production was studied in osteoarthritis (OA)- and rheumatoid arthritis (RA)-FLS, involved in Th1/Th17 differentiation. The effect of VIP was also determined. IL-17RA, IL-17RC, IL-12p35 and IL-23p19 expression was measured by real-time polymerase chain reaction. IL-12 and IL-23 protein levels were measured by ELISA in supernatant cultures. Results: TNF alpha, LPS and poly(I:C) induced an increase in IL-17RA in RA-FLS, whereas TNF alpha, TNF alpha plus IL-17 and poly(I:C) enhanced IL-17RC transcripts in FLS. VIP diminished the upregulated expression of IL-17RA in RA-FLS following TNF alpha and poly(I:C). TNF alpha, LPS and poly(I:C) increased IL-12 and IL-23 levels in cells derived from patients presenting both pathologies. However, IL-17A decreased IL-12 and augmented IL-23. VIP decreased IL-12p35 mRNA up-regulation by poly(I:C) and IL-23p19 transcripts in LPS-treated FLS. Conclusions: Inflammatory cytokines and TLR ligands modulate IL-17R, IL-12 and IL-23 possibly favoring the cross talk between FLS and Th1/Th17 cells. The ability of VIP to counteract the enhancing effect of proinflammatory molecules on IL-17R and the IL-12 family of cytokines corroborates and amplifies the beneficial effect of this endogenous neuroimmunopeptide in rheumatic diseases.