| First Author | Lukkarinen H | Year | 2009 |
| Journal | Am J Respir Cell Mol Biol | Volume | 41 |
| Issue | 1 | Pages | 59-68 |
| PubMed ID | 19097983 | Mgi Jnum | J:161580 |
| Mgi Id | MGI:4459631 | Doi | 10.1165/rcmb.2008-0179OC |
| Citation | Lukkarinen H, et al. (2009) Matrix metalloproteinase-9 deficiency worsens lung injury in a model of bronchopulmonary dysplasia. Am J Respir Cell Mol Biol 41(1):59-68 |
| abstractText | Increased activity of matrix metalloproteinase (MMP)-9 is associated with the development of bronchopulmonary dysplasia (BPD) in newborn infants, but the role of MMP-9 in the pathophysiology of BPD is unclear. We have shown that perinatal expression of interleukin-1 beta (IL-1 beta) in the lung is sufficient to cause a BPD-like illness in infant mice. To study the hypothesis that MMP-9 is an important downstream mediator in IL-1 beta-induced lung injury in the newborn, we compared the effects of IL-1 beta on fetal and postnatal lung inflammation and development in transgenic mice with regulatable pulmonary overexpression of human mature IL-1 beta with wild-type (IL-1 beta/MMP-9(+/+)) or null (IL-1 beta/MMP-9(-/-)) MMP-9 loci. IL-1 beta increased the expression of MMP-9 mRNA and amount of MMP-9 protein in the lungs of MMP-9(+/+) mice. IL-1 beta/MMP-9(-/-) mice had fewer neutrophils but more macrophages in the lungs than did IL-1 beta/MMP-9(+/+) mice. MMP-9 deficiency increased pulmonary cell death and macrophage clearance of dying cells in IL-1 beta-expressing mice. IL-1 beta/MMP-9(-/-) mice had more severe alveolar hypoplasia than IL-1 beta/MMP-9(+/+) mice, implying that IL-1 beta-induced lung disease was worsened in the absence of MMP-9. These results suggest that MMP-9 activity in the inflamed neonatal lung protects the lung against injury. |
