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Updated: May 8, 2026
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
MMP28 promotes macrophage polarization toward M2 cells and augments pulmonary fibrosis
Sina A Gharib1, Laura K Johnston1, Isham Huizar2
1*Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington, USA
Abstract:
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.
Insights
Matrix metalloproteinase-28 (MMP28) regulates macrophage polarization, promoting anti-inflammatory M2 cell function. Loss of MMP28 reduces M2 polarization and protects against lung fibrosis.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Matrix metalloproteinases (MMPs) are crucial in innate immunity, regulating leukocyte trafficking and activation.
- MMP28 (epilysin) is expressed by macrophages and influences their lung recruitment.
- The role of MMP28 in macrophage polarization and subsequent fibrotic responses remains largely unexplored.
Purpose of the Study:
- To investigate the role of MMP28 in regulating macrophage polarization.
- To determine if MMP28-dependent changes in macrophage polarization impact lung fibrotic responses.
- To elucidate the function of MMP28 in both experimental models of lung inflammation and pulmonary fibrosis.
Main Methods:
- Gene expression analysis of wild-type (WT) and Mmp28-/- bone marrow-derived macrophages (BMDMs) stimulated with LPS (M1) or IL-4/IL-13 (M2).
- Macrophage polarization assessment in lungs of WT and Mmp28-/- mice exposed to Pseudomonas aeruginosa.
- Evaluation of macrophage polarization, weight loss, and collagen levels in WT and Mmp28-/- mice during bleomycin-induced pulmonary fibrosis.
Main Results:
- MMP28 dampens pro-inflammatory macrophage activity and promotes M2 programming.
- Mmp28-/- mice exhibited deficits in M2 polarization in both in vivo models.
- Reduced M2 polarization in Mmp28-/- mice was associated with protection from bleomycin-induced lung fibrosis.
Conclusions:
- MMP28 is a key regulator of macrophage polarization, favoring M2 function.
- MMP28 deficiency leads to impaired M2 polarization and confers protection against pulmonary fibrosis.
- These findings reveal a novel role for MMP28 in macrophage biology and the pathogenesis of lung diseases.