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Thrombospondin 1 activates the macrophage Toll-like receptor 4 pathway

Yanzhang Li1, Xinyu Qi, Xiaopeng Tong

  • 11] Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA [2] Current address: College of Medicine, Henan University, Kaifeng 475004, China.

Cellular & Molecular Immunology
|August 20, 2013
PubMed

Insights

Thrombospondin 1 (TSP1) activates macrophages by stimulating Toll-like receptor 4 (TLR4) and nuclear factor-kappaB (NF-κB) pathways. This macrophage activation by TSP1 is partly mediated through its receptor, CD36.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophages play a critical role in inflammatory responses.
  • Thrombospondin 1 (TSP1) has been previously shown to influence macrophage inflammatory phenotypes.

Purpose of the Study:

  • To elucidate the mechanisms by which TSP1 regulates macrophage function.
  • To investigate the role of TSP1 in macrophage activation pathways.

Main Methods:

  • Treatment of bone marrow-derived macrophages with recombinant or purified TSP1.
  • Assessment of tumor-necrosis factor-alpha (TNF-α) expression.
  • Measurement of Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activity.
  • Utilizing TLR4-deficient macrophages and in vivo models.
  • Blocking the TSP1-CD36 interaction with peptides or antibodies.

Main Results:

  • TSP1 treatment dose- and time-dependently stimulated TNF-α expression in macrophages.
  • TSP1 upregulated both mRNA and protein levels of TLR4 and enhanced NF-κB activity.
  • TSP1-induced TNF-α production was abrogated in TLR4-deficient macrophages.
  • TSP1 also stimulated TLR4 activation in macrophages in vivo.
  • Blocking the TSP1-CD36 interaction attenuated TSP1-mediated macrophage activation.

Conclusions:

  • TSP1 activates macrophages through a pathway dependent on TLR4.
  • The interaction between TSP1 and its receptor CD36 partially mediates TSP1-induced macrophage activation via the TLR4 pathway.

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