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Interaction of matrix with integrin receptors is required for optimal LPS-induced MAP kinase activation

Martha M Monick1, Linda Powers, Noah Butler

  • 1Department of Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA. martha-monick@uiowa.edu

American Journal of Physiology. Lung Cellular and Molecular Physiology
|July 13, 2002
PubMed

Insights

Macrophage activation by lipopolysaccharide (LPS) requires integrin receptors for optimal signaling. Blocking integrin function reduces LPS-induced inflammatory responses, highlighting their complementary role alongside Toll-like receptor 4.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophages respond to lipopolysaccharide (LPS) via Toll-like receptor 4 (TLR4).
  • Other surface molecules may influence TLR-mediated signaling.
  • Integrin receptors have been implicated in LPS signaling pathways.

Purpose of the Study:

  • To investigate the role of macrophage integrin receptors in mitogen-activated protein (MAP) kinase activation by LPS.
  • To determine if integrin signaling is necessary for optimal LPS-induced inflammatory mediator production.

Main Methods:

  • Macrophages were cultured on non-adherent conditions or treated with integrin inhibitors (EDTA, RGD peptides).
  • LPS-induced signaling was assessed by measuring whole cell protein tyrosine phosphorylation.
  • Activation of extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) MAP kinases was quantified.
  • LPS-induced tumor necrosis factor-alpha (TNF-α) production was measured.

Main Results:

  • Reduced macrophage adherence decreased LPS-induced tyrosine phosphorylation and MAP kinase activation (ERK, JNK).
  • Inhibition of integrin signaling significantly reduced LPS-induced MAP kinase activity.
  • Blocking integrin signaling led to decreased LPS-induced TNF-α production.

Conclusions:

  • Optimal LPS signaling in macrophages requires complementary input from integrin receptors, in addition to TLR4.
  • Integrin receptors play a crucial role in mediating LPS-induced inflammatory responses.
  • Targeting integrin signaling may offer a strategy to modulate macrophage activation in inflammatory conditions.

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