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

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:
  • Journal of immunology

دوره 188 11  شماره 

صفحات  -

تاریخ انتشار 2012