Increased matrix metalloproteinase-9 concentration and activity after stimulation with interleukin-17 in mouse airways

Prause, O.; Bozinovski, S.; Anderson, G. P.; Lindeń, A.
April 2004
Thorax;Apr2004, Vol. 59 Issue 4, p313
Academic Journal
Background: The proteolytic enzyme matrix metalloproteinase (MMP)-9 can degrade structural compounds such as the extracellular matrix and the basement membrane in the airways and lungs. MMP-9 has therefore been implicated in remodelling of the airways and lungs during severe asthma and chronic obstructive pulmonary disease (COPD). Methods: The effect of the T lymphocyte derived proinflammatory cytokine interleukin (II)- 17 on MMP-9 protein release and activity in the airways was studied in vivo and in vitro. Results: In vivo, intranasal stimulation of mice with 11-17 induced the release of the precursor molecule proMMP-9 in bronchoalveolar lavage (BAL) fluid, associated with a pronounced local accumulation of neutrophils that stained positive hr MMP-9. Stimulation with 11-17 also increased the concentration of free soluble MMP-9 that was proteolytically active as determined by a gelatinase substrate assay. The concentration of MMP-9 in ML fluid had a strong positive correlation with the number of neutrophils; the amount of MMP-9 per neutrophil was not increased by 11-17 stimulation. In vitro, stimulation of mouse neutrophils with 11-17 did not increase the concentration of proMMP-9 in the conditioned medium. Conclusion: Local stimulation with 11-17 increases the concentration of biologically active MMP-9 as well as its precursor molecule in mouse airways in vivo. This increase in proteolytic load is probably mainly due to an increased number of neutrophils and not to an increase in the release of MMP-9 from each neutrophil. These findings indicate a link between the I lymphocyte cytokine 11-17 and increased proteolytic load in the airways which may be relevant for chronic inflammatory airway diseases such as severe asthma and COPD.


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