MMP-12 regulates proliferation of mouse macrophages via the ERK/P38 MAPK pathways during inflammation

Exp Cell Res. 2019 May 15;378(2):182-190. doi: 10.1016/j.yexcr.2019.03.018. Epub 2019 Mar 14.

Abstract

MMP-12 is a metalloproteinase (MMP) mainly secreted by macrophages and regulating the degradation of the extracellular matrix. MMP-12 is related to several diseases such as emphysema, myocardial infarction and liver fibrosis. However, the functions associated with inflammation of MMP-12 in macrophages have not yet been fully investigated. Therefore, the aim of this study is to elucidate the role of MMP-12 in mouse macrophages during inflammation. Here we show by flow cytometry that MMP-12 was closely associated with the number of F4/80 + macrophages from mouse liver following exposure to LPS. Pro-inflammatory cytokines as well as the proliferation of RAW 264.7 cell line was modulated by MMP-12 knock down as illustrated by qRT-PCR, flow cytometry, CCK-8, Western Blot and EdU staining assays. Furthermore, down-regulation of MMP-12 decreased the expression and the phosphorylation levels of P38 and ERK1/2. Taken together, these data show that MMP-12 contributes to the proliferation of mouse macrophages as well as the secretion of IL-1β, IL-6, TNF-α, CXCL1 and CXCL3 through the ERK/P38 MAPK signaling pathway.

Keywords: Inflammation; MAPK signaling pathway; MMP-12; Macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cytokines / immunology
  • Flow Cytometry
  • Gene Knockdown Techniques
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Inflammation Mediators / immunology
  • Lipopolysaccharides
  • Liver / metabolism
  • Liver / pathology
  • MAP Kinase Signaling System*
  • Macrophages* / drug effects
  • Macrophages* / immunology
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 12 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • RAW 264.7 Cells

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Matrix Metalloproteinase 12
  • matrix metallopeptidase 12, mouse