RT Journal Article T1 Inflammatory mediators alter interleukin-17 receptor, interleukin-12 and -23 expression in human osteoarthritic and rheumatoid arthritis synovial fibroblasts: Immunomodulation by vasoactive intestinal peptide A1 Carrión Caballo, Mar A1 Pérez García, Selene A1 Jimeno, Rebeca A1 Juarranz Moratilla, Yasmina A1 González Álvaro, Isidoro A1 Pablos Álvarez, José Luis A1 Gutiérrez Cañas, Irene A1 Pérez Gomáriz, Rosa María AB 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 (TNF) 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 Th1Th17 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, LPS and poly(I:C) induced an increase in IL-17RA in RA-FLS, whereas TNF, TNF 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 and poly(I:C). TNF, 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 upregulation 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 Th1Th17 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. PB Karger Publishers SN 1021-7401 YR 2013 FD 2013 LK https://hdl.handle.net/20.500.14352/93435 UL https://hdl.handle.net/20.500.14352/93435 LA eng NO Mar Carrión, Selene Pérez-García, Rebeca Jimeno, Yasmina Juarranz, Isidoro González-Álvaro, José Luis Pablos, Irene Gutiérrez-Cañas, Rosa P. Gomariz; 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 1 August 2013; 20 (5): 274–284. https://doi.org/10.1159/000350892 NO Instituto de Salud Carlos III NO Comunidad de Madrid NO European Commission DS Docta Complutense RD 5 abr 2025