The melanocortin receptor agonist NDP-MSH impairs the allostimulatory function of dendritic cells.
As alpha-melanocyte-stimulating hormone (alpha-MSH) is released by immunocompetent cells and has potent immunosuppressive properties, it was determined whether human dendritic cells (DCs) express the receptor for this hormone. Reverse transcription-polymerase chain reaction detected messenger RNA specific for all of the known melanocortin receptors in DCs. Mixed lymphocyte reactions also revealed that treatment with [Nle(4), DPhe(7)]-alpha-MSH (NDP-MSH), a potent alpha-MSH analogue, significantly reduced the ability of DCs to stimulate allogeneic T cells. The expression of various cell surface adhesion, maturation and costimulatory molecules on DCs was also investigated. Although treatment with NDP-MSH did not alter the expression of CD83 and major histocompatibility complex class I and II, the surface expression of CD86 (B7.2), intercellular adhesion molecule (ICAM-1/CD54) and CD1a was reduced. In summary, our data indicate that NDP-MSH inhibits the functional activity of DCs, possibly by down-regulating antigen-presenting and adhesion molecules and that these events may be mediated via the extracellular signal-regulated kinase 1 and 2 pathway.
Rennalls
La'Verne P
LP
Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, UK. laverner@icr.ac.uk
Seidl
Thomas
T
Larkin
James M G
JM
Wellbrock
Claudia
C
Gore
Martin E
ME
Eisen
Tim
T
Bruno
Ludovica
L
D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous; D000521:alpha-MSH / Q000494:pharmacology*
D018949:Antigens, CD1; D051940:B7-2 Antigen; C419393:CD1a antigen; C497964:CD86 protein, human; D012333:RNA, Messenger; D044101:Receptors, Melanocortin; D018799:Intercellular Adhesion Molecule-1; D000521:alpha-MSH; D019950:Mitogen-Activated Protein Kinase 1