Superoxide dismutase mimetic reduces hypoxia-induced O2*-, TGF-beta, and VEGF production by macrophages.


Journal Article

Normal tissue injury poses a major limitation to the success of radiation therapy (RT) in the treatment of solid tumors. We propose that radiation-induced lung injury is a result of chronic oxidative stress propagated by hypoxia-induced macrophage activation and cytokine production. Therefore, the objective of our study was two-fold. First, in vivo studies were conducted to support our hypothesis suggesting radiation injury is characterized by chronic hypoxia associated with increased macrophage infiltration/activation and pro-fibrogenic/angiogenic cytokine production. Second, we investigated the proposed mechanism of radiation injury in vitro. We demonstrate that hypoxia (0.5% O2) elicits macrophages to produce higher levels of O2*-, TGF-beta, and VEGF than normoxia. Our hypothesis that O2*- is contributing to increased macrophage cytokine production was supported by a significant reduction in TGF-beta and VEGF when redox signaling was minimized using a small molecular weight metalloporphyrin antioxidant, MnTE-2-PyP5+ .

Full Text

Duke Authors

Cited Authors

  • Jackson, IL; Chen, L; Batinic-Haberle, I; Vujaskovic, Z

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 41 / 1

Start / End Page

  • 8 - 14

PubMed ID

  • 17164174

Pubmed Central ID

  • 17164174

International Standard Serial Number (ISSN)

  • 1071-5762

Digital Object Identifier (DOI)

  • 10.1080/10715760600913150


  • eng

Conference Location

  • England