Protective role of reactive oxygen species in endotoxin-induced lung inflammation through modulation of IL-10 expression.

Abstract

Reactive oxygen species (ROS) generated by NADPH oxidase are generally known to be proinflammatory, and it seems to be counterintuitive that ROS play a critical role in regulating the resolution of the inflammatory response. However, we observed that deficiency of the p47(phox) component of NADPH oxidase in macrophages was associated with a paradoxical accentuation of inflammation in a whole animal model of noninfectious sepsis induced by endotoxin. We have confirmed this observation by interrogating four separate in vivo models that use complementary methodology including the use of p47(phox-/-) mice, p47(phox-/-) bone marrow chimera mice, adoptive transfer of macrophages from p47(phox-/-) mice, and an isolated perfused lung edema model that all point to a relationship between excessive acute inflammation and p47(phox) deficiency in macrophages. Mechanistic data indicate that ROS deficiency in both cells and mice results in decreased production of IL-10 in response to treatment with LPS, at least in part, through attenuation of the Akt-GSK3-β signal pathway and that it can be reversed by the administration of rIL-10. Our data support the innovative concept that generation of ROS is essential for counterregulation of acute lung inflammation.

• Authors: Jing Deng, Xuerong Wang, Feng Qian, Stephen Vogel, Lei Xiao, Ravi Ranjan, Hyesuk Park, Manjula Karpurapu, Richard D Ye, Gye Young Park, John W Christman
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 11 Pg. 5734-40 (Jun 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22547702 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Endotoxins
• IL10 protein, human
• Reactive Oxygen Species
• Recombinant Proteins
• Interleukin-10
• Luciferases
• NADPH Oxidases
• neutrophil cytosolic factor 1

Topics

• Adoptive Transfer
• Animals
• Disease Models, Animal
• Endotoxins (antagonists & inhibitors, toxicity)
• Gene Expression Regulation (immunology)
• Humans
• Interleukin-10 (antagonists & inhibitors, biosynthesis)
• Luciferases (biosynthesis, genetics)
• Lung (immunology, metabolism, pathology)
• Macrophages, Peritoneal (transplantation)
• Mice
• Mice, Knockout
• Mice, Transgenic
• NADPH Oxidases (deficiency, genetics)
• Pneumonia (immunology, pathology, therapy)
• Reactive Oxygen Species (metabolism, therapeutic use)
• Recombinant Proteins (administration & dosage)