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The role of endothelial interleukin‐8/NADPH oxidase 1 axis in sepsis
Author(s) -
Miyoshi Takashi,
Yamashita Kouhei,
Arai Toshiyuki,
Yamamoto Kokichi,
Mizugishi Kiyomi,
Uchiyama Takashi
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03303.x
Subject(s) - nox1 , lipopolysaccharide , gene knockdown , nadph oxidase , umbilical vein , sepsis , microbiology and biotechnology , tumor necrosis factor alpha , immunology , stimulation , pathogenesis , nox4 , biology , reactive oxygen species , chemistry , endocrinology , apoptosis , biochemistry , in vitro
Summary Sepsis is a generalized inflammatory disease, caused by the hyperinflammatory response of the host, rather than by invading organisms. Endothelial cells play a crucial role in the pathogenesis of sepsis. In this study, we investigated the effects of interleukin‐8 (IL‐8), a known neutrophil chemoattractant, on lipopolysaccharide (LPS) ‐induced reactive oxygen species (ROS) production by endothelial cells, and its significance in the pathogenesis of LPS‐mediated sepsis. The results revealed that IL‐8 directly induced ROS production in human umbilical vein endothelial cells (HUVECs), and also mediated LPS‐induced ROS production by HUVECs. Stimulation of HUVECs by LPS strongly enhanced tissue factor expression, a hallmark of severe sepsis, which was suppressed by IL‐8 knockdown. We further discovered that NADPH oxidase (Nox) 1 expression in LPS‐stimulated HUVECs was markedly repressed by IL‐8 knockdown, and Nox1 knockdown reduced tissue factor expression, suggesting that the LPS/IL‐8 signalling in endothelial cells was predominantly mediated by Nox1. In conclusion, LPS stimulation of endothelial cells causes activation of the IL‐8–Nox1 axis, enhances the production of ROS, and ultimately contributes to the progression of severe sepsis.