POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation.

摘要: To investigate the relevance of adrenocorticotrophic hormone (ACTH) therapy in human gouty arthritis, we have tested effect several ACTH-related peptides a murine model experimental gout. Systemic treatment mice with ACTH4-10 (MEHFRWG) (10-200 microgram s. c.) inhibited neutrophil accumulation without altering peripheral blood cell counts or circulating corticosterone levels. A similar was seen alpha- and beta-melanocyte stimulating hormones (1-30 s.c.). In vivo release chemokine KC-(detected lavage fluids before maximal influx neutrophils) significantly reduced (-50 to -60%) by ACTH4-10. Macrophage activation vitro, determined as phagocytosis KC release, ACTH approximate IC50 values 30 nM 100 microM, respectively. The melanocortin receptor type 3/4 antagonist SHU9119 prevented inhibitory actions both vitro vivo. However, 3, but not 4, mRNA detected mouse peritoneal macrophages RT-PCR. Therefore, propose that this related amino acid sequences attenuates (and possibly production other cytokines) from consequent inhibition host inflammatory response, thus providing notional anti-inflammatory mechanism for is unrelated stimulation glucocorticoid release.