Tofacitinib Decreases Autophagy of Fibroblast-Like Synoviocytes From Rheumatoid Arthritis Patients

• DOI: 10.3389/fphar.2022.852802
• Publication Date: 2022-03-03T10:56:37Z
• Authors: M. Vomero; M. Caliste; C. Barbati; M. Speziali; A. I. Celia; F. Ucci; C. Ciancarella; E. Putro; T. Colasanti; G. Buoncuore; E. Corsiero; M. Bombardieri; F. R. Spinelli; F. Ceccarelli; F. Conti; C. Alessandri
• Keywords: Pharmacology; 0301 basic medicine; autophagy; 0303 health sciences; 03 medical and health sciences; tofacitinib; apoptosis; janus tyrosine kinases; Therapeutics. Pharmacology; RM1-950; Rheumatoid arthritis; rheumatoid arthritis; apoptosis; autophagy; janus tyrosine kinases; tofacitinib; 3. Good health

The pathway of Janus tyrosine kinases (JAKs) has a central role in the pathogenesis Rheumatoid Arthritis (RA) by regulating multiple immune functions and cytokine production. JAK inhibitor tofacitinib is effective RA patients not responding to methotrexate or TNF-inhibitors. Since hyperactive autophagy been associated with impaired apoptosis fibroblast-like synoviocytes (FLS), we aimed investigate modulating these cells. FLS isolated from biopsies were cultured presence inducer rapamycin serum deprivation condition. Levels autophagy, apoptosis, citrullinated proteins analyzed western blot, flow cytometry, immunocytofluorescence, Real-Time PCR. Rapamycin induced an increase RA-FLS while levels marker LC3-II reduced after vitro treatment tofacitinib. analysis autophagic flux specific fluorescence dye confirmed reduction FLS. did influence Modulation process significantly change citrullination. results this study demonstrate that able modulate contributing its effectiveness patients.