title: The role of hyaluronic acid in SEB-induced acute lung inflammation.
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.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Georgia 31207, USA.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Uchakina
authors.forename: Clara M
authors.initials: CM
authors.lastname: Castillejo
authors.forename: Christy C
authors.initials: CC
authors.lastname: Bridges
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McKallip
mesh_terms: D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology* / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D014453:Glucuronosyltransferase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000276:immunology* / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D018836:Inflammation Mediators; D010455:Peptides; C575521:glycyl-alanyl-histidyl-tryptophyl-glutaminyl-phenylalanyl-asparagyl-alanyl-leucyl-threonyl-valyl-arginine; C031818:enterotoxin B, staphylococcal; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase