Autocrine alpha-melanocyte-stimulating hormone inhibits NF-kappa B activation in human glioma

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) modulates inflammation by inhibiting production of proinflammatory cytokines. Using a plasmid vector encoding alpha-MSH, we examined whether autocrine alpha-MS H inhibits activation of the nuclear transcription factor NF-kappa B, a fac tor that is essential to expression of proinflammatory cytokines, in human glioma cells (A-172). Electrophoretic mobility shift assays of nuclear extr acts demonstrated that NF-kappa B activation induced by lipopolysaccharide was inhibited in glioma cells transfected with alpha-MSH vector. Western bl ot analysis revealed that this inhibition was linked to preservation of exp ression of I kappa B alpha protein, Chloramphenicol acetyltransferase assay indicated that NF-kappa B-dependent reporter gene expression was suppresse d in A-172 cells transfected with alpha-MSH vector. Finally, fluorescence s taining confirmed that A-172 cells bear alpha-MSH receptors, The findings a re consistent with the idea that, in central nervous system (CNS) inflammat ion, autocrine alpha-MSH exerts anti-inflammatory actions via modulation of NF-kappa B activation by preservation of I kappa B alpha protein, Based on this action of the peptide, it should be possible to treat neurodegenerati ve disease, stroke, encephalitis, trauma, and other CNS disorders that have an inflammatory component through gene therapy,vith alpha-MSH vector. J. N eurosci. Res, 58:684-689, 1999. (C) 1999 Wiley-Liss, Inc.