REGULATION OF THE MANGANESE SUPEROXIDE-DISMUTASE AND INDUCIBLE NITRIC-OXIDE SYNTHASE GENE IN RAT NEURONAL AND GLIAL-CELLS

Bidirectional communication occurs between neuroendocrine and immune s ystems through the action of various cytokines. Responses to various i nflammatory mediators include increases in intracellular reactive oxyg en species (ROS), notably, superoxide anion (O-2(-)) and nitric oxide (NO.). Neurotoxicity mediated by NO. may result from the reaction of N O. with O-2, leading to formation of peroxynitrite (ONOO-). ROS are hi ghly toxic, potentially contributing to extensive neuronal damage. We, therefore, evaluated the effects of a variety of inflammatory mediato rs on the regulation of mRNA levels for manganese superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS) in primary culture s of rat neuronal and glial cells. To determine age-dependent variatio n of mRNA expression, we used glial cells derived from newborn, 3-, 21 -, and 95-day-old rat brains. Interleukin-1 beta, interferon-gamma (IF N-gamma), bacterial lipopolysaccharide (LPS), and tumor necrosis facto r-alpha showed significant induction of MnSOD in both glial and neuron al cells. However, only LPS and IFN-gamma increased iNOS mRNA. These d ata demonstrate that these two genes are similarly regulated in two ce lls of the nervous system, further suggesting that the oxidative state of a cell may dictate a neurotoxic or neuroprotective outcome.