title: Transforming growth factor (TGF)-β signalling is increased in rheumatoid synovium but TGF-β blockade does not modify experimental arthritis.
abstract: The aim of this study was to analyse the distribution of regulatory and inhibitory mothers against decapentaplegic homologue (Smad) proteins as markers of active transforming growth factor (TGF)-β signalling in rheumatoid arthritis (RA) synovial tissue and to investigate the effect of TGF-β blockade in the development and progression of collagen-induced arthritis. The expression of Smad proteins in synovial tissues from RA, osteoarthritic and healthy controls was analysed by immunohistochemistry. Arthritis was induced in DBA/1 mice by immunization with chicken type-II collagen (CII). TGF-β was blocked in vivo with the specific peptide p17 starting at the time of immunization or on the day of arthritis onset. T cell population frequencies and specific responses to CII were analysed. The expression of cytokines and transcription factors was quantified in spleen and joint samples. Statistical differences between groups were compared using the Mann-Whitney U-test or one-way analysis of variance (anova) using the Kruskal-Wallis test. p-Smad-2/3 and inhibitory Smad-7 expression were detected in RA and control tissues. In RA, most lymphoid infiltrating cells showed nuclear p-Smad-2/3 without Smad-7 expression. Treatment with TGF-β antagonist did not affect clinical severity, joint inflammation and cartilage damage in collagen-induced arthritis. Frequency of T cell subsets, mRNA levels of cytokines and transcription factors, specific proliferation to CII, serum interleukin (IL)-6 and anti-CII antibodies were comparable in p17 and phosphate-buffered saline (PBS)-treated groups. The pattern of Smad proteins expression demonstrates active TGF-β signalling in RA synovium. However, specific TGF-β blockade does not have a significant effect in the mice model of collagen-induced arthritis.
authors.affiliation: Hospital 12 de Octubre, 'i+12', Instituto de Investigación, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Gonzalo-Gil
authors.forename: G
authors.initials: G
authors.lastname: Criado
authors.forename: B
authors.initials: B
authors.lastname: Santiago
authors.forename: J
authors.initials: J
authors.lastname: Dotor
authors.forename: J L
authors.initials: JL
authors.lastname: Pablos
authors.forename: M
authors.initials: M
authors.lastname: Galindo
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D030161:Avian Proteins / Q000276:immunology; D002645:Chickens; D024043:Collagen Type II / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007114:Immunization; D007150:Immunohistochemistry; D051379:Mice; D008811:Mice, Inbred DBA; D023421:Models, Animal; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051785:Smad Proteins / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; D024043:Collagen Type II; C562050:P17 peptide; D010455:Peptides; D051785:Smad Proteins; D016212:Transforming Growth Factor beta
keywords: Th17; Treg; collagen-induced arthritis; rheumatoid arthritis; transforming growth factor-beta (TGF-β)