Role of immunoregulators in nitric oxide production in hypoxia-induced apoptosis in alveolar cells

Interleukin 1β (IL-1β), Tumor necrosis factor α (TNF-α), and Interferon γ (IFN-γ) cytokines stimulate nitric oxide production due to inflammation manifested by apoptosis and hypoxia. We proposed that extent of inflammation leading to hypoxia initially and programmed cell death later both can enhance the Magnetic Resonance Imaging (MRI) visible edema fluid content in breast and lung tumors due to oxygen and energy insufficiency in inflammatory tumor epithelial cells. The mechanism of A549 cell damage due to nitric oxide (NO) production included: Cytokines regulated NO synthase regulation through the activation of nuclear factor κB (NF-κB); Cofactor tetrahydrobiopterin (BH4)-catalyzed synthesis of inducible nitric oxide synthase (iNOS). The NO production and increased NO synthase lead to Na+ ion transport and cell proliferation with differentiation or apoptosis. Our recent report on hypoxia-induced apoptosis and decreased cell proliferation with differentiation supported the possibility of MRI as potential technique in alveolar and tumor imaging of inflammation. Hypoxic cells showed the possibility of NO production associated with their viability and rapid increase of apoptosis. High resolution MRI can track this high inflammation, tumor angiogenesis regions in tumors. In conclusion, acute NO production can be a cause of hypoxia induced apoptosis and possibly MRI visible indicator of inflamed tumor viability.