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

Martha M Monick; Linda Powers; Noah Butler; Timur Yarovinsky; Gary W Hunninghake

doi:10.1152/ajplung.00437.2001

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

Journal article

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

Martha M Monick, Linda Powers, Noah Butler, Timur Yarovinsky and Gary W Hunninghake

American journal of physiology. Lung cellular and molecular physiology, Vol.283(2), pp.L390-L402

08/01/2002

DOI: 10.1152/ajplung.00437.2001

PMID: 12114201

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Abstract

Exposure of macrophages to endotoxin [lipopolysaccharide (LPS)] results in a cascade of events resulting in the release of multiple inflammatory and anti-inflammatory mediators. The Toll-like receptor (TLR) 4 complex is the major receptor that mediates LPS signaling. However, there is evidence that other surface molecules may play a complementary role in the TLR-induced events. Integrin receptors are one class of receptors that have been linked to LPS signaling. This study investigates the role of macrophage integrin receptors in the activation of mitogen-activated protein (MAP) kinases by LPS. In conditions where macrophages were not permitted to adhere to matrix or a tissue culture surface, we found a decrease in LPS signaling as documented by a marked reduction in tyrosine phosphorylation of whole cell proteins. This was accompanied by a significant decrease in extracellular signal-regulated kinase and c-Jun NH2-terminal kinase MAP kinase activation. Inhibition of integrin signaling, with EDTA or RGD peptides, decreased LPS-induced MAP kinase activity. The functional consequence of blocking integrin signaling was demonstrated by decreased LPS-induced tumor necrosis factor-α production. These observations demonstrate that, in addition to the TLR receptor complex, optimal LPS signaling requires complementary signals from integrin receptors.

Details

Title: Subtitle: Interaction of matrix with integrin receptors is required for optimal LPS-induced MAP kinase activation
Creators: Martha M Monick - Department of Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242
Linda Powers - Department of Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242
Noah Butler - Department of Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242
Timur Yarovinsky - Department of Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242
Gary W Hunninghake - Department of Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.283(2), pp.L390-L402
DOI: 10.1152/ajplung.00437.2001
PMID: 12114201
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Language: English
Date published: 08/01/2002
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001146602771

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