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- W2160331316 abstract "RATIONALE: Collagen is an extracellular matrix protein involved in airway fibrosis and has been implicated in the pathogenesis of airway remodeling in asthma. We have previously demonstrated that IL-13 increased collagen type 1 alpha 2 (COL1A2) mRNA and protein expression in human airway fibroblasts from asthmatic patients compared to normal controls. Our data has shown that this IL-13 induced expression may be attenuated using a non-specific Matrix Metalloproteinase (MMP) inhibitor suggesting that MMPs mediate IL-13 induced collagen expression. Since MMP2 is an important enzyme for extracellular remodeling, we investigated the effects of MMP2 inhibition on IL-13 induced COL1A2 expression in airway fibroblasts isolated from subjects with human asthma. METHODS: In an ongoing study, 5 subjects with mild asthma (PC20 FEV1 0.6 ± 0.14 mg/ml) and 5 normal control subjects (PC20 FEV1 > 16 mg/ml) underwent bronchoscopy with endobronchial biopsy. Quiescent airway fibroblasts were treated with IL-13 (50 ng/ml) in the presence and absence of an MMP2 inhibitor (40μM) for 24 and 48 hours, respectively. Total RNA was extracted and COL1A2 and MMP2 mRNA expression was quantified using RT-PCR. RESULTS: IL-13 induces MMP2 mRNA expression and the addition of an MMP2 inhibitor to IL-13 treated fibroblasts significantly suppressed COL1A2 mRNA expression in asthma patients compared to normal controls at 24 and 48 hours (p<0.05). CONCLUSIONS: We demonstrate that MMP2 inhibition significantly reduces IL-13 induced ex vivo mRNA expression of COL1A2 in human asthma. This novel finding implicates the role of MMP2 in modulating IL-13 induced airway fibrosis in chronic asthma." @default.
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- W2160331316 date "2011-02-01" @default.
- W2160331316 modified "2023-09-27" @default.
- W2160331316 title "MMP-2 Inhibition Attenuates IL-13 Induced Collagen Type-1 mRNA Expression in Human Airway Fibroblasts in Asthma" @default.
- W2160331316 doi "https://doi.org/10.1016/j.jaci.2010.12.509" @default.
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