Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo

Autor: S. L. Yancy, Riley S. Rees, Daniel G. Remick, Michael J. Welsh, T. Yamada, Sahoko Hirano, J. Hata, Robert R. Gilmont
Rok vydání: 2004
Předmět:
Lipopolysaccharides
Male
Time Factors
Health
Toxicology and Mutagenesis
HSP27 Heat-Shock Proteins
urologic and male genital diseases
Toxicology
Rats
Sprague-Dawley
Edema
Tissue Distribution
Phosphorylation
Lung
Cells
Cultured
Heat-Shock Proteins
Kinase
Immunohistochemistry
Cell biology
Neoplasm Proteins
Endothelial stem cell
medicine.anatomical_structure
embryonic structures
Tumor necrosis factor alpha
endocrine system
animal structures
Endothelium
p38 mitogen-activated protein kinases
macromolecular substances
Biology
Lung injury
Permeability
Hsp27
Sepsis
medicine
Animals
RNA
Messenger
Dose-Response Relationship
Drug
Tumor Necrosis Factor-alpha
Myocardium
Cell Biology
Hydrogen Peroxide
Blotting
Northern
Precipitin Tests
Actins
Rats
Pulmonary Alveoli
Disease Models
Animal
biology.protein
RNA
Endothelium
Vascular
Zdroj: Cell biology and toxicology. 20(1)
ISSN: 0742-2091
Popis: Lung edema during sepsis is triggered by formation of gaps between endothelial cells followed by macrophage infiltration. Endothelial gap formation has been proposed to involve changes in the structure of the actin filament cytoskeleton. Heat shock protein 27 (HSP27) is believed to modulate actin filament dynamics or structure, in a manner dependent on its phosphorylation status. We hypothesized that HSP27 may play a role in endothelial gap formation, by affecting actin dependent events in endothelial cells. As there has been no report concerning HSP27 in lung edemain vivo, we examined induction and phosphorylation of HSP27 in lung following LPS injection, as a model of sepsis. In lung, HSP27 mainly localized in capillary endothelial cells of the alveolus, and in smooth muscle cells of pulmonary arteries. HSP27 became significantly more phosphorylated at 3 h after LPS treatment, while the distribution of HSP27 remained unchanged. Pre-treatment with anti-TNFα antibody, which has been shown to reduce lung injury, blocked increases in HSP27 phosphorylation at 3 h. HSP27 phosphorylation was also increased in cultured rat pulmonary arterial endothelial cells (RPAEC) by treatment with TNFα, LPS, or H2O2. This phosphorylation was blocked by pre-treatment with SB203580, an inhibitor of the upstream kinase, p38 MAP kinase. Increased endothelial permeability caused by H2O2 in vitro was also blocked by SB203580. The amount of actin associated with HSP27 was reduced after treatment with LPS, or H2O2. In summary, HSP27 phosphorylation temporally correlated with LPS induced pathological endothelial cell gap formationin vivo and in a cell culture model system. This is the first report of increased HSP27 phosphorylation associated with pathological lung injury in an animal model of sepsis.
Databáze: OpenAIRE
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