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Mechanisms of the Antiinflammatory Effects of α‐MSH: Role of Transcription Factor NF‐κB and Adhesion Molecule Expression
Author(s) -
KALDEN D.H.,
SCHOLZEN T.,
BRZOSKA T.,
LUGER T. A.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08682.x
Subject(s) - cell adhesion molecule , transcription factor , chemistry , nf κb , vcam 1 , microbiology and biotechnology , alpha (finance) , nfkb1 , inflammation , icam 1 , signal transduction , biology , immunology , biochemistry , medicine , gene , construct validity , nursing , patient satisfaction
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.