Autocrine α-melanocyte-stimulating hormone inhibits NF-κB activation in human glioma

The neuropeptide α-melanocyte-stimulating hormone (α-MSH) modulates inflammation by inhibiting production of proinflammatory cytokines. Using a plasmid vector encoding α-MSH, we examined whether autocrine α-MSH inhibits activation of the nuclear transcription factor NF-κB, a factor that is essential to expression of proinflammatory cytokines, in human glioma cells (A-172). Electrophoretic mobility shift assays of nuclear extracts demonstrated that NF-κB activation induced by lipopolysaccharide was inhibited in glioma cells transfected with α-MSH vector. Western blot analysis revealed that this inhibition was linked to preservation of expression of IκBα protein. Chloramphenicol acetyltransferase assay indicated that NF-κB-dependent reporter gene expression was suppressed in A- 172 cells transfected with α-MSH vector. Finally, fluorescence staining confirmed that A-172 cells bear α-MSH receptors. The findings are consistent with the idea that, in central nervous system (CNS) inflammation, autocrine α-MSH exerts anti-inflammatory actions via modulation of NF-κB activation by preservation of IκBα protein. Based on this action of the peptide, it should be possible to treat neurodegenerative disease, stroke, encephalitis, trauma, and other CNS disorders that have an inflammatory component through gene therapy with α-MSH vector.