Mechanisms of the Antiinflammatory Effects of α‐MSH: Role of Transcription Factor NF‐κB and Adhesion Molecule Expression

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Abstract
The recruitment of leukocytes from the circulation to inflamed tissue is regulated by the expression of adhesion molecules on both leukocytes and endothelial cells. The proopiomelanocortin-derived peptide α-melanocyte stimulating hormone (α-MSH) is known to modulate inflammation. Thus, we investigated the influence of α-MSH on the LPS-induced expression of the adhesion molecules E-selectin and VCAM-1 on endothelial cells. Human microvascular endothelial cells (HMEC-1) were treated with LPS (100 ng/ml) alone or in the presence of α-MSH (10−8 to 10−16 M). RT-PCR analysis showed that α-MSH significantly reduced LPS-induced expression of VCAM-1 and E-selectin. Since many adhesion molecules contain regulatory NF-κB sites in their promoter region, the role of α-MSH in the activation of the transcription factor NF-αB was also investigated. α-MSH significantly downregulated the LPS-mediated activation of NF-κB, in a dose-dependent manner. These findings indicate that modulation of the transcription factor NF-κB is a crucial molecular event, one that seems to be responsible for the antiinflammatory effects of α-MSH.