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Melanocortin receptor signaling in RAW264.7 macrophage cell line
Connie W Lam1, Mauro Perretti, Stephen J Getting
1Research 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.
Abstract:
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.
