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TNF-α induces matrix metalloproteinase-9-dependent soluble intercellular adhesion molecule-1 release via

Chia-Lan Tsai, Wei-Chung Chen, Hsi-Lung Hsieh

  • 1Department of Physiology and Pharmacology and Health Ageing Research Center, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. chuenmao@mail.cgu.edu.tw.

Journal of Biomedical Science
|February 8, 2014
PubMed
Abstract

Insights

Tumor necrosis factor-alpha (TNF-α) increases matrix metalloproteinase-9 (MMP-9) in bone cells via c-Src, MAPKs, and NF-κB signaling. This MMP-9 production may contribute to soluble ICAM-1 release, impacting bone inflammatory diseases.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Matrix metalloproteinase-9 (MMP-9) is implicated in bone inflammatory diseases.
  • Tumor necrosis factor-alpha (TNF-α) induces MMP-9, but the underlying mechanisms in MC3T3-E1 cells are not fully understood.

Purpose of the Study:

  • To elucidate the signaling pathways by which TNF-α up-regulates MMP-9 expression in MC3T3-E1 cells.
  • To investigate the relationship between TNF-α-induced MMP-9 and soluble ICAM-1 (sICAM-1) production.

Main Methods:

  • Gelatin zymography, Western blot, RT-PCR, and real-time PCR were used to assess MMP-9 expression.
  • Pharmacological inhibitors (e.g., PP1, U0126, SB202190, SP600125, Bay11-7082) and siRNAs targeting signaling molecules were employed.
  • Promoter assays, immunoprecipitation, and ELISA were utilized to analyze signaling pathways and sICAM-1 release.

Main Results:

  • TNF-α-induced MMP-9 expression and promoter activity were inhibited by targeting c-Src, MAPKs (ERK, p38, JNK), and NF-κB pathways.
  • TNF-α stimulated the formation of TNFR1, TRAF2, and c-Src complexes.
  • NF-κB phosphorylation and translocation were induced by TNF-α and inhibited by Bay11-7082.
  • TNF-α-induced MMP-9 upregulation correlated with sICAM-1 release.

Conclusions:

  • TNF-α up-regulates MMP-9 expression in MC3T3-E1 cells through c-Src, MAPKs, and NF-κB signaling cascades.
  • TNF-α-induced MMP-9 may promote the release of sICAM-1.
  • The interplay between MMP-9 and sICAM-1 is potentially significant in regulating bone inflammatory diseases.

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