Regulation of angiopoietin expression by bacterial lipopolysaccharide

American Journal of Physiology - Lung Cellular and Molecular Physiology - Tập 294 Số 5 - Trang L955-L963 - 2008
Mahroo Mofarrahi1, Thamer Nouh, Salman T. Qureshi, Loïc Guillot2, Dominique Mayaki, Sabah N. A. Hussain
1Critical Care Division, Royal Victoria Hospital, 687 Pine Ave West, Montréal, Québec, Canada H3A 1A1.
2McGill University = Université McGill [Montréal, Canada]

Tóm tắt

Angiopoietins are ligands for Tie-2 receptors and play important roles in angiogenesis and inflammation. While angiopoietin-1 (Ang-1) inhibits inflammatory responses, angiopoietin-2 (Ang-2) promotes cytokine production and vascular leakage. In this study, we evaluated in vivo and in vitro effects of Escherichia coli lipopolysaccharides (LPS) on angiopoietin expression. Wild-type C57/BL6 mice were injected with saline (control) or E. coli LPS (20 mg/ml ip) and killed 6, 12, and 24 h later. The diaphragm, lung, and liver were excised and assayed for mRNA and protein expression of Ang-1, Ang-2, and Tie-2 protein and tyrosine phosphorylation. LPS injection elicited a severalfold rise in Ang-2 mRNA and protein levels in the three organs. By comparison, both Ang-1 and Tie-2 levels in the diaphragm, liver, and lung were significantly attenuated by LPS administration. In addition, Tie-2 tyrosine phosphorylation in the lung was significantly reduced in response to LPS injection. In vitro exposure to E. coli LPS elicited cell-specific changes in Ang-1 expression, with significant induction in Ang-1 expression being observed in cultured human epithelial cells, whereas significant attenuation of Ang-1 expression was observed in response to E. coli LPS exposure in primary human skeletal myoblasts. In both cell types, E. coli LPS elicited substantial induction of Ang-2 mRNA, a response that was mediated in part through NF-κB. We conclude that in vivo endotoxemia triggers functional inhibition of the Ang-1/Tie-2 receptor pathway by reducing Ang-1 and Tie-2 expression and inducing Ang-2 levels and that this response may contribute to enhanced vascular leakage in sepsis.

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American Journal of Physiology - Lung Cellular and Molecular Physiology

Tập 294 Số 5

L955-L963

Thông tin tác giả