Dexamethasone inhibits BAFF expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis.
Fibroblast-like synoviocytes (FLS) play a major role in the pathogenesis of rheumatoid arthritis (RA). FLS isolated from patients with RA (FLS-RA) express B cell-activating factor belonging to the TNF family (BAFF), a cytokine that has been associated with the onset and progression of RA. Glucocorticoids are powerful anti-inflammatory drugs used in the treatment of RA. In the present study, we examined the effect of dexamethasone (Dex) on constitutive and TNF-alpha- and IFN-gamma-induced BAFF expression in FLS-RA. BAFF mRNA expression and soluble BAFF were determined by RT-PCR and ELISA, respectively. The results showed that constitutive BAFF mRNA expression was inhibited by Dex in a dose- and time-dependent manner. Also, Dex inhibited the secretion of BAFF in a time-dependent manner reaching 76% of inhibition 72 h after treatment. Moreover, Dex suppressed both mRNA and protein BAFF expression induced by TNF-alpha but had no effect on IFN-gamma-induced BAFF expression. In comparison with B cells cultured alone, B cells co-cultured with FLS-RA exhibited a higher survival, which was inhibited when FLS-RA were pretreated with Dex. However, the enhanced B cell survival was reestablished by the addition of rhBAFF. Therefore, Dex is a potent inhibitor of constitutive and TNF-alpha-induced BAFF expression in FLS-RA.
Reyes
Lilian I
LI
Instituto de Ciencias, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo. Av. Las Condes 12438, Lo Barnechea, Santiago, Chile. Electronic address: lireyes@uchile.cl.
León
Francisca
F
Instituto de Ciencias, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo. Av. Las Condes 12438, Lo Barnechea, Santiago, Chile. Electronic address: fleonb@udd.cl.
González
Patricia
P
Instituto de Ciencias, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo. Av. Las Condes 12438, Lo Barnechea, Santiago, Chile. Electronic address: patty_bq@yahoo.com.
Rozas
María F
MF
Instituto de Ciencias, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo. Av. Las Condes 12438, Lo Barnechea, Santiago, Chile. Electronic address: mafercita@gmail.com.
Labarca
Cristián
C
Clínica Alemana, Av. Vitacura 5951, Vitacura, Santiago, Chile; Hospital Padre Hurtado, Esperanza 2150, San Ramón, Santiago, Chile. Electronic address: clabarcasolar@gmail.com.
Segovia
Alejandra
A
Clínica Alemana, Av. Vitacura 5951, Vitacura, Santiago, Chile. Electronic address: asegovia@alemana.cl.
Neira
Oscar
O
Clínica Alemana, Av. Vitacura 5951, Vitacura, Santiago, Chile; Hospital del Salvador, Universidad de Chile, Av. Salvador 364, Providencia, Santiago, Chile. Electronic address: oneira@mi.cl.
Naves
Rodrigo
R
Instituto de Ciencias, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo. Av. Las Condes 12438, Lo Barnechea, Santiago, Chile; Facultad de Ciencias de la Salud, Universidad Pedro de Valdivia, Av. Tobalaba 1275, Providencia, Santiago, Chile. Electronic address: rnaves@upv.cl.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000893:Anti-Inflammatory Agents; D053264:B-Cell Activating Factor; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma