The role of hyaluronic acid in SEB-induced acute lung inflammation

Clin Immunol. 2013 Jan;146(1):56-69. doi: 10.1016/j.clim.2012.11.002. Epub 2012 Nov 14.

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.

MeSH terms

  • Acute Disease
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Line
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Enterotoxins / immunology*
  • Enterotoxins / toxicity
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / immunology
  • Glucuronosyltransferase / metabolism
  • Hyaluronan Synthases
  • Hyaluronic Acid / immunology*
  • Hyaluronic Acid / metabolism
  • Hyaluronoglucosaminidase / genetics
  • Hyaluronoglucosaminidase / immunology
  • Hyaluronoglucosaminidase / metabolism
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Lung / drug effects
  • Lung / immunology*
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Peptides / pharmacology
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Pneumonia / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Cytokines
  • Enterotoxins
  • Inflammation Mediators
  • Peptides
  • glycyl-alanyl-histidyl-tryptophyl-glutaminyl-phenylalanyl-asparagyl-alanyl-leucyl-threonyl-valyl-arginine
  • enterotoxin B, staphylococcal
  • Hyaluronic Acid
  • Glucuronosyltransferase
  • Hyaluronan Synthases
  • Hyaluronoglucosaminidase