TGFβ-induced matrix production by bronchial fibroblasts in asthma: budesonide and formoterol effects.

摘要: To investigate the mechanisms of enhanced airway deposition subepithelial collagen in asthma and its sensitivity to drug therapy with combination an inhaled glucocorticosteroid (GC) a long-acting β(2)-agonist (LABA), cell model system involving bronchial fibroblasts derived from biopsies patients stable mild-to-moderate has been used. mimic unstable conditions severe asthma, were stimulated ex vivo TGFβ1. Primary established central 8 asthmatic incubated for 24 h 0.4% serum or TGFβ1 (10 ng/ml) with/without GC budesonide (BUD; 10 nM) and/or LABA formoterol (FORM; 0.1 nM). Procollagen peptide I (PICP), metalloproteinase (MMP)-1 tissue inhibitor MMPs (TIMP-1) determined culture media using ELISA while activity MMP-2, -3, -9 by zymography. Metabolically labeled proteoglycans, biglycan decorin, associated fibrillation/deposition, separated chromatography SDS-PAGE. The levels PICP increased 2-fold (p < 0.05). BUD FORM reduced increase 58% 0.01) 36% 0.05) each alone had no effect. Decorin most patients; completely counteracted this decrease. TIMP-1 not affected drugs. These results suggest that therapy, without affecting metalloproteolytic balance, potential counteract production normalize small proteoglycans which may affect fibrillation deposition.