Abstract
We investigated the role of the extracellular matrix component, hyaluronic acid (HA) in SEB-induced ALI/ARDS. Intranasal exposure of mice to SEB led to a significant increase in the level of soluble hyaluronic acid in the lungs. Similarly, in an endothelial cell/spleen cell co-culture, SEB exposure led to significant increases in soluble levels of hyaluronic acid, cellular proliferation, and cytokine production compared with SEB-exposed spleen cells or endothelial cells alone. Exposure of SEB-activated spleen cells to hyaluronic acid led to increased cellular proliferation and increased cytokine production. SEB-induced cytokine production and proliferation in vitro were significantly reduced by the hyaluronic acid blocking peptide, Pep-1. Finally, treatment of SEB-exposed mice with Pep-1 significantly reduced SEB-induced ALI/ARDS, through reduction of cytokine production and numbers of lung inflammatory cells, compared to mice treated with a control peptide. Together, these results suggest the possibility of targeting HA for the treatment of SEB-induced ALI/ARDS.
Copyright © 2012 Elsevier Inc. All rights reserved.
MeSH terms
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Acute Disease
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Animals
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Bronchoalveolar Lavage Fluid / chemistry
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Bronchoalveolar Lavage Fluid / immunology
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Cell Line
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Cell Proliferation / drug effects
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Cells, Cultured
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Coculture Techniques
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Cytokines / genetics
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Cytokines / immunology
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Cytokines / metabolism
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Endothelial Cells / drug effects
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Endothelial Cells / immunology
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Endothelial Cells / metabolism
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Enterotoxins / immunology*
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Enterotoxins / toxicity
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Enzyme-Linked Immunosorbent Assay
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Female
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Flow Cytometry
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Glucuronosyltransferase / genetics
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Glucuronosyltransferase / immunology
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Glucuronosyltransferase / metabolism
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Hyaluronan Synthases
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Hyaluronic Acid / immunology*
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Hyaluronic Acid / metabolism
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Hyaluronoglucosaminidase / genetics
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Hyaluronoglucosaminidase / immunology
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Hyaluronoglucosaminidase / metabolism
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Inflammation Mediators / immunology
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Inflammation Mediators / metabolism
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Lung / drug effects
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Lung / immunology*
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Lung / metabolism
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Mice
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Mice, Inbred C57BL
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Peptides / pharmacology
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Pneumonia / chemically induced
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Pneumonia / immunology*
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Pneumonia / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
Substances
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Cytokines
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Enterotoxins
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Inflammation Mediators
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Peptides
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glycyl-alanyl-histidyl-tryptophyl-glutaminyl-phenylalanyl-asparagyl-alanyl-leucyl-threonyl-valyl-arginine
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enterotoxin B, staphylococcal
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Hyaluronic Acid
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Glucuronosyltransferase
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Hyaluronan Synthases
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Hyaluronoglucosaminidase