Matrix Metalloproteinase-9 Deficiency Impairs Cellular Infiltration and Bronchial Hyperresponsiveness during Allergen-Induced Airway Inflammation

Abstract

We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and their corresponding wild-type (WT) littermates. After a single intraperitoneal sensitization to ovalbumin, the mice were exposed daily either to ovalbumin (1%) or phosphate-buffered saline aerosols from days 14 to 21. Significantly less peribronchial mononuclear cell infiltration of the airways and less lymphocytes in the bronchoalveolar lavage fluid were detected in challenged MMP-9(-/-) as compared to WT mice. In contrast, comparable numbers of bronchoalveolar lavage fluid eosinophils were observed in both genotypes. After allergen exposure, the WT mice developed a significant airway hyperresponsiveness to carbachol whereas the MMP-9(-/-) mice failed to do so. Allergen exposure induced an increase of MMP-9-related gelatinolytic activity in WT lung extracts. Quantitative reverse transcriptase-polymerase chain reaction showed increased mRNA levels of MMP-12, MMP-14, and urokinase-type plasminogen activator after allergen exposure in the lung extracts of WT mice but not in MMP-9-deficient mice. In contrast, the expression of tissue inhibitor of metalloproteinases-1 was enhanced after allergen exposure in both groups. We conclude that MMP-9 plays a key role in the development of airway inflammation after allergen exposure.

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

“…MMP-12 mRNA levels have been shown to increase in the lungs of mice subjected to allergens exposure as compared to sham exposed counterparts [29]. MMP-12 deficient mice display less inflammation than wild type mice [30] and show a less important peribronchial fibrosis when challenged repetitively for 3 months with allergens ( Fig.…”

“…As an additional problem linked to the lack of specificity of inhibitors, different related MMPs can display opposite effects. As an exemple, MMP-9 and MMP-12 have been found to actively participate in the pathological remodeling process during asthma [29,103] while MMP-8 seems to play an opposite role since its deficiency promotes allergen-induced airway inflammation [104].…”

Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production

“…Mice were sacrificed, and a bronchoalveolar lavage was immediately performed using 4 × 1 ml PBS-EDTA 0.05 mM (Calbiochem, Darmstadt, Germany) as previously described [13,14]. Cells were recovered by gentle manual aspiration.…”

Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC)

“…Proteins were isolated from tumour and control tissues by urea extraction (Cataldo et al, 2002). Samples were migrated on a 12% polyacrylamide gel and transferred to a PVDF membrane (Perkin Elmer Life Sciences Inc., Boston, MA, USA).…”