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

Chenyu Guan1, Yudong Xiao1, Kan Li1

  • 1Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56th Lingyuanxi Road, Guangzhou, Guangdong, 510055, China; Guangdong Province Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China.

Experimental Cell Research
|March 19, 2019
PubMed

Insights

Matrix metalloproteinase-12 (MMP-12) promotes macrophage proliferation and pro-inflammatory cytokine release during inflammation. Knocking down MMP-12 reduces inflammation via the ERK/P38 MAPK pathway.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinase-12 (MMP-12) is secreted by macrophages and degrades the extracellular matrix.
  • MMP-12 is implicated in diseases like emphysema, myocardial infarction, and liver fibrosis.
  • The specific role of MMP-12 in macrophage-mediated inflammation requires further investigation.

Purpose of the Study:

  • To elucidate the function of MMP-12 in mouse macrophages during inflammatory responses.
  • To investigate the signaling pathways regulated by MMP-12 in macrophages.

Main Methods:

  • Flow cytometry to quantify F4/80+ macrophages in mouse liver after LPS exposure.
  • Gene knockdown of MMP-12 in RAW 264.7 cell line.
  • Quantitative real-time PCR (qRT-PCR) and Western Blotting to assess gene and protein expression.
  • Cell proliferation assays (CCK-8) and EdU staining.
  • Analysis of signaling pathway components (P38 and ERK1/2 phosphorylation).

Main Results:

  • MMP-12 expression correlated with the number of F4/80+ macrophages in LPS-exposed mouse liver.
  • MMP-12 knockdown modulated pro-inflammatory cytokine production (IL-1β, IL-6, TNF-α, CXCL1, CXCL3) and RAW 264.7 cell proliferation.
  • Down-regulation of MMP-12 decreased the expression and phosphorylation of P38 and ERK1/2 signaling molecules.

Conclusions:

  • MMP-12 plays a significant role in promoting mouse macrophage proliferation.
  • MMP-12 contributes to the secretion of key pro-inflammatory cytokines.
  • These effects are mediated through the regulation of the ERK/P38 MAPK signaling pathway.
Keywords:
InflammationMAPK signaling pathwayMMP-12Macrophage

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