Original ContributionGenetic deficiency of NADPH oxidase does not diminish, but rather enhances, LPS-induced acute inflammatory responses in vivo
Section snippets
Animals and experimental procedures
Age-and body weight-matched female C57BL/6J wild-type (WT), gp91phox−/−, and p47phox−/− mice at 10–12 weeks of age weighing 20–22 g were purchased from The Jackson Laboratory (Bar Harbor, ME, USA). The mice were housed under specific-pathogen-free conditions and in a temperature-and humidity-controlled environment (12-h light/dark cycle) with unlimited access to tap water and food. Mice were acclimated for 7–10 days before initiation of experiments. All animal procedures were reviewed and
Deficiency of gp91phox or p47phox does not diminish the LPS-induced increase in serum levels of inflammatory mediators
We first determined the effect of LPS on systemic inflammation in WT mice, as assessed by increased serum levels of inflammatory mediators. As shown in Fig. 1, Fig. 2, LPS treatment induced a time-and dose-dependent increase in serum concentrations of sVCAM-1, sICAM-1, MCP-1, and TNFα. TNFα peaked at 1 h, and the other inflammatory molecules were significantly increased at 3 h (Fig. 1). sVCAM-1 and sICAM-1 remained elevated up to 24 h, whereas MCP-1 and TNFα gradually returned to baseline after
Discussion
Increased ROS production and oxidative stress during endotoxemia are thought to causally contribute to cell and tissue injury, systemic sepsis syndrome, and septic shock and death [4], [25], [28], [29], [30]. ROS also modulate a number of cell signaling pathways resulting in transcription factor activation [17], [18]. Recent studies have suggested that NADPH oxidase-derived ROS (NOX-ROS) act as second messengers mediating LPS-induced inflammatory responses [16], [17], [29], [31], [32], [33].
Acknowledgment
This publication was made possible by Grant P01 AT002034 (B.F./W.J.Z.) from the National Center for Complementary and Alternative Medicine (NCCAM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCCAM or the National Institutes of Health.
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