In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics

Back ground: Corticos teroid s play an impor tant ro le in inflamm ation and remodel ling of a irways and are consider ed an impor tant therape utic target in asthm a. Inflamm ation in asthm a is cha racterized by a dysregul ation of eosino-phil apop tosis and of marker s of airway s remodel ling. We evaluated the ability of fluni solide to inh ibit in vitro the relea se of metallopr oteina ses-9 (MMP-9 ), tissue inhibi tor metallopr oteina ses-1 (TIMP -1), trans form ing grow th fact or (TGF- b ) an d fibr onecti n by sputum cells (SC) as well as to indu ce sputum eosinoph il a poptosi s. Method s: The SC, isolated from induced sputum samples of 12 mil d-to-mod erate asthm atics, wer e cultur ed for 24 h in the presence or absence of fluni solide (1, 10 and 100 l M). The relea se of mediators was assessed by enzyme- linked immu nosorbent assay (ELIS A) whereas apoptosi s was studi ed by TU NEL techni que. Result s: Flunisol ide (10 lM) signi ficantl y redu ced MMP-9 and TIMP -1 ( P ¼ 0.0011 an d P < 0.0001 respect ively) an d increa sed M MP-9/TI MP-1 mo lar ratio ( P ¼ 0.004) . In addition, flunisol ide de creased TGF -b and fibr onectin relea se by SC (P ¼ 0.006; an d P < 0.0001 respectivel y) and increa sed eosinop hil apop tosis ( P < 0.001). Conc lusions: Thes e resul ts demonst rate that fluni solide may play an impor tant role in the inhibi tion of airway inflamm ation and remod elling, by pr omoting the resol ution of eosinop hilic inflamm ation an d by inhibiting the release of MMP -9, TIMP -1, TGF- b and fibronectin.