ISSN:
1365-2222
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background Allergic rhinitis (AR) is an inflammatory disease characterized by nasal wall remodelling with intense infiltration of eosinophils and mast cells/basophils. Matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are the major proteolytic enzymes that induce airway remodelling. These enzymes are also important in the migration of inflammatory cells through basement membrane components.Objective We evaluated whether fexofenadine hydrochloride (FEX), the carboxylic acid metabolite of terfenadine with selective H1-receptor antagonist activity, could inhibit MMP production from nasal fibroblasts (NFs) in response to TNF-α stimulation in vitro.Methods NFs were established from nasal polyp-derived fibroblasts (PFs) taken from patients with AR. Nasal mucosal fibroblasts (MFs) were also induced from nasal mucosal tissues from septal deformity patients without allergy. PF and MF (2 × 105 cells/mL, each) were stimulated with TNF-α in the presence of various concentrations of FEX. After 24 h, culture supernatants were obtained and assayed for MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 levels by ELISA. The influence of FEX on mRNA expression of MMPs and TIMPs in 4 h-cultured cells was also evaluated by real-time RT-PCR. Furthermore, nuclear factor-κB (NF-κB) activation in fibroblasts treated with FEX for 4 h was examined by ELISA.Results FEX at more than 350 ng/mL inhibited the production of MMP-2 and MMP-9 from both PF and MF in response to TNF-α stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected by FEX. FEX also inhibited MMP mRNA expression and NF-κB activation in PF and MF after TNF-α stimulation.Conclusion The present data suggest that the attenuating effect of FEX on MMP-2 and -9 production from NFs induced by inflammatory stimulation may underlie the therapeutic mode of action of the agent on allergic diseases, including AR.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-2222.2004.02127.x
