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NPJ Biofilms Microbiomes. 2017 Nov 13;3:31. doi: 10.1038/s41522-017-0039-9. eCollection 2017.

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.

Author information

1
Laboratory of Diabetes and Diabetes Related Research, US, USA.
2
Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY USA.
3
Hofstra Northwell School of Medicine, Hempstead, NY USA.
4
National Institutes of Health, Bethesda, Baltimore, MD USA.
5
Department of Emergency Medicine, Manhasset, NY USA.
6
Icahn School of Medicine at Mount Sinai, New York, NY USA.
7
University of Muenster, Münster, Germany.
8
University Teaching Hospital, Luenburg, Germany.
9
Johns Hopkins University School of Medicine, Baltimore, MD USA.
10
Cedars-Sinai Medical Center, Los Angeles, CA USA.
11
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.
12
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
13
Albert Einstein College of Medicine, Bronx, NY USA.
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Contributed equally

Abstract

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.

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