NF-kappaB activation is inhibited in human pulmonary epithelial cells transfected with alpha-melanocyte-stimulating hormone vector.

alpha-Melanocyte-stimulating hormone (alpha-MSH) modulates inflammation. We investigated the influence of alpha-MSH on NF-kappaB activation in human pulmonary epithelial cells (A549) using a plasmid vector encoding alpha-MSH (pCMV-ssMSH). Electrophoretic mobility shift assays demonstrated that NF-kappaB activation induced by lipopolysaccharide was inhibited in A549 cells transfected with pCMV-ssMSH. Western blot analysis revealed that this inhibition was linked to preservation of expression of IkappaBalpha protein. Chloramphenicol acetyltransferase assay indicated that NF-kappaB-dependent reporter gene expression was suppressed in A549 cells transfected with pCMV-ssMSH. The findings indicate that anti-inflammatory actions are exerted via modulation of NF-kappaB activation by preservation of IkappaBalpha protein in human pulmonary epithelial cells transfected with alpha-MSH vector. We showed a possibility of gene therapy for chronic inflammatory lung diseases.