Fiche publication
Date publication
janvier 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak
,
Dr PFEFFER Sébastien
,
Pr GOTTENBERG Jacques-Eric
Tous les auteurs :
Alsaleh G, Francois A, Philippe L, Gong YZ, Bahram S, Cetin S, Pfeffer S, Gottenberg JE, Wachsmann D, Georgel P, Sibilia J
Lien Pubmed
Résumé
We evaluated micro (mi) RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i) synovial fibroblasts (FLS) isolated from healthy controls (N) or Rheumatoid Arthritis (RA) patients; (ii) human dermal fibroblasts (HDF) isolated from healthy controls (N) or Systemic Sclerosis (SSc) patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C) or IFN-gamma treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-gamma. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C) or IFN-gamma. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C)- and IFN-gamma-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C)- and IFN-gamma-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc.
Référence
PLoS One. 2014 Oct 31;9(10):e111266
