title: Differential expression of MMP-2 and -9 and their inhibitors in fetal lung cells exposed to mechanical stretch: regulation by IL-10.
abstract: OBJECTIVE
  Abnormal remodeling of the extracellular matrix (ECM) has been implicated in the pathogenesis of bronchopulmonary dysplasia. However, the contribution of lung parenchymal cells to ECM remodeling after mechanical injury is not well defined. The objective of these studies was to investigate in vitro the release of MMP-2 and -9 and their respective inhibitors TIMP-2 and -1, and to explore potential regulation by IL-10.
  
  
  METHODS
  Mouse fetal epithelial cells and fibroblasts isolated on E18-19 of gestation were exposed to 20% cyclic stretch to simulate lung injury. MMP-2 and MMP-9 activity were investigated by zymography and ELISA. TIMP-1 and TIMP-2 abundance were analyzed by Western blot.
  
  
  RESULTS
  We found that mechanical stretch increased MMP-2 and decreased TIMP-2 in fibroblasts, indicating that excessive stretch promotes MMP-2 activation, expressed as the MMP-2/TIMP-2 ratio. Incubation with IL-10 did not change MMP-2 activity. In contrast, mechanical stretch of epithelial cells decreased MMP-9 activity and the MMP-9/TIMP-1 ratio by 60-70%. When IL-10 was added, mechanical stretch increased the MMP-9/TIMP-1 ratio by 50%.
  
  
  CONCLUSIONS
  We conclude that mechanical stretch differentially affects MMP-2/9 and their inhibitors in fetal lung cells. IL-10 modulates MMP-9 activity through a combination of effects on MMP-9 and TIMP-1 levels.
authors.affiliation: Department of Pediatrics, Women & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI 02905, USA.
authors.forename: Renda L
authors.initials: RL
authors.lastname: Hawwa
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hokenson
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.forename: Zheping
authors.initials: Z
authors.lastname: Huang
authors.forename: Surendra
authors.initials: S
authors.lastname: Sharma
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchez-Esteban
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000378:metabolism*; D008168:Lung / Q000201:enzymology* / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016753:Interleukin-10; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9