Mechanisms of the antiinflammatory effects of alpha-MSH. Role of transcription factor NF-kappa B and adhesion molecule expression.
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 alpha-melanocyte stimulating hormone (alpha-MSH) is known to modulate inflammation. Thus, we investigated the influence of alpha-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 alpha-MSH (10(-8) to 10(-16) M). RT-PCR analysis showed that alpha-MSH significantly reduced LPS-induced expression of VCAM-1 and E-selectin. Since many adhesion molecules contain regulatory NF-kappa B sites in their promoter region, the role of alpha-MSH in the activation of the transcription factor NF-alpha B was also investigated. alpha-MSH significantly downregulated the LPS-mediated activation of NF-kappa B, in a dose-dependent manner. These findings indicate that modulation of the transcription factor NF-kappa B is a crucial molecular event, one that seems to be responsible for the antiinflammatory effects of alpha-MSH.
Kalden
D H
DH
Ludwig Boltzmann Institute of Cellbiology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Germany.
Scholzen
T
T
Brzoska
T
T
Luger
T A
TA
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation; D008833:Microcirculation; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply; D014158:Transcription, Genetic; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D000521:alpha-MSH / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D000521:alpha-MSH