Melanocortin receptor signaling in RAW264.7 macrophage cell line.
Melanocortin peptides modulate cytokine release and adhesion molecule expression. Here we have investigated the early cell-signaling pathway responsible for the induction of interleukin-10 (IL-10) in RAW264.7 cells. Cell incubation with ACTH(1-39) or MTII (melanotan II) did not alter ERK1/2 and JNK phosphorylation, while p38 phosphorylation and intracellular cAMP accumulation occurred within minutes. ACTH(1-39) and MTII provoked a time-dependent accumulation of IL-10 that was abrogated by the PKA inhibitor H-89 and only partially blocked by the p38 MAPK inhibitor SB203580. Thus, in RAW264.7 cells, IL-10 induction by the melanocortins is via the PKA pathway, and this mechanism could contribute to their anti-inflammatory profile.
Lam
Connie W
CW
Research Centre in Biochemical Pharmacology, The William Harvey Research Institute, Bart's and The London, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Perretti
Mauro
M
Getting
Stephen J
SJ
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases; D016753:Interleukin-10 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D010456:Peptides, Cyclic / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
D010456:Peptides, Cyclic; D044101:Receptors, Melanocortin; C079282:melanotan-II; D016753:Interleukin-10; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases