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J Leukoc Biol. 2014 Jan;95(1):9-18. doi: 10.1189/jlb.1112587. Epub 2013 Aug 20.

MMP28 promotes macrophage polarization toward M2 cells and augments pulmonary fibrosis.

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*Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington, USA
†Division of Pulmonary and Critical Care Medicine, Texas Tech University Health Science Center, Lubbock, Texas, USA
Correspondence: Center for Lung Biology, Div. of Pulmonary and Critical Care Medicine, University of Washington, 850 Republican Ave., Seattle, WA 98109, USA. E-mail:

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Members of the MMP family function in various processes of innate immunity, particularly in controlling important steps in leukocyte trafficking and activation. MMP28 (epilysin) is a member of this family of proteinases, and we have found that MMP28 is expressed by macrophages and regulates their recruitment to the lung. We hypothesized that MMP28 regulates other key macrophage responses, such as macrophage polarization. Furthermore, we hypothesized that these MMP28-dependent changes in macrophage polarization would alter fibrotic responses in the lung. We examined the gene expression changes in WT and Mmp28-/- BMDMs, stimulated with LPS or IL-4/IL-13 to promote M1 and M2 cells, respectively. We also collected macrophages from the lungs of Pseudomonas aeruginosa-exposed WT and Mmp28-/- mice to evaluate changes in macrophage polarization. Lastly, we evaluated the macrophage polarization phenotypes during bleomycin-induced pulmonary fibrosis in WT and Mmp28-/- mice and assessed mice for differences in weight loss and total collagen levels. We found that MMP28 dampens proinflammatory macrophage function and promots M2 programming. In both in vivo models, we found deficits in M2 polarization in Mmp28-/- mice. In bleomycin-induced lung injury, these changes were associated with reduced fibrosis. MMP28 is an important regulator of macrophage polarization, promoting M2 function. Loss of MMP28 results in reduced M2 polarization and protection from bleomycin-induced fibrosis. These findings highlight a novel role for MMP28 in macrophage biology and pulmonary disease.


M1; epilysin; inflammation; monocytes

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