New melanocortin-like peptide of E. coli can suppress inflammation via the mammalian melanocortin-1 receptor (MC1R): possible endocrine-like function for microbes of the gut

作者：Qiang Xiaoling; Liotta Anthony S; Shiloach Joseph; Gutierrez J C; Wang Haichao; Ochani Mahendar; Ochani Kanta; Yang Huan; Rabin Aviva; LeRoith Derek; Lesniak Maxine A; Boehm Markus; Maaser Christian; Kannengiesser Klaus; Donowitz Mark; Rabizadeh Shervin; Czura Christopher J; Tracey Kevin J; Westlake Mark; Zarfeshani Aida; Mehdi Syed F; Danoff Ann; Ge Xueliang; Sanyal Suparna; Schwartz Gary J; Roth Jesse^*

来源：npj Biofilms and Microbiomes, 2017, 3(1): UNSP 31.

DOI：10.1038/s41522-017-0039-9

E. coli releases a 33 amino acid peptide melanocortin-like peptide of E. coli (MECO-1) that is identical to the C-terminus of the E. coli elongation factor-G (EF-G) and has interesting similarities to two prominent mammalian melanocortin hormones, alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH). Note that MECO-1 lacks HFRW, the common pharmacophore of the known mammalian melanocortin peptides. MECO-1 and the two hormones were equally effective in severely blunting release of cytokines (HMGB1 and TNF) from macrophage-like cells in response to (i) endotoxin (lipopolysaccharide) or (ii) pro-inflammatory cytokine HMGB-1. The in vitro anti-inflammatoty effects of MECO-1 and of alpha-MSH were abrogated by (i) antibody against melanocortin-1 receptor (MC1R) and by (ii) agouti, an endogenous inverse agonist of MC1R. In vivo MECO-1 was even more potent than alpha-MSH in rescuing mice from death due to (i) lethal doses of LPS endotoxin or (ii) cecal ligation and puncture, models of sterile and infectious sepsis, respectively.

• 出版日期2017-11-13
• 单位河北医科大学; NIH