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• W2006496081 abstract "Background: Macrophage elastase (MMP-12) is involved in the inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate in mice the effect of MMP-12 inhibition on the inflammatory process induced by cigarette smoke (CS) or by lipopolysaccharide (LPS) exposure of the airways. Experimental approach: C57BL/6 mice were given, orally, either the selective MMP-12 inhibitor AS111793 (3, 10, 30 and 100 mg kg−1), the PDE-4 inhibitor roflumilast (3 mg kg−1) or vehicle, then exposed to CS (for 3 days) or to LPS (100 μg mL−1, 30 min). Subsequent to the last smoke or LPS exposure, bronchoalveolar lavages (BAL) were performed and lungs were removed and homogenized to analyze various markers of inflammation at appropriate times. Key results: Inhibition of MMP-12 by AS111793 (10 and 30 mg kg−1) was associated with a reduction of the increase in neutrophil number in BAL fluids after 4 days and of macrophages after 11 days. On day 4, AS111793 also significantly reduced all the inflammation markers that had increased after CS exposure, including soluble TNF receptors I and II, MIP-1γ, IL-6 and pro-MMP-9 activity in BAL fluids, and KC/CXCL1, fractalkine/CX3CL1, TIMP-1 and I-TAC/CXCL11 in lung parenchyma. In contrast, inhibition of MMP-12 did not reduce neutrophil influx, pro-MMP-9 activity or KC/CXCL1 release in BAL fluids of mice exposed to LPS. Conclusion: Inhibition of MMP-12 with AS111793, reduced the inflammatory process associated with exposure of mice to CS, strongly suggesting a specific involvement of MMP-12 in lung inflammation following CS exposure. British Journal of Pharmacology (2008) 154, 1206–1215; doi:10.1038/bjp.2008.180; published online 19 May 2008" @default.
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• W2006496081 date "2008-07-01" @default.
• W2006496081 modified "2023-09-25" @default.
• W2006496081 title "The selective MMP-12 inhibitor, AS111793 reduces airway inflammation in mice exposed to cigarette smoke" @default.
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• W2006496081 doi "https://doi.org/10.1038/bjp.2008.180" @default.
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