TY - JOUR
T1 - New melanocortin-like peptide of E. coli can suppress inflammation via the mammalian melanocortin-1 receptor (MC1R)
T2 - Possible endocrine-like function for microbes of the gut
AU - Qiang, Xiaoling
AU - Liotta, Anthony S.
AU - Shiloach, Joseph
AU - Gutierrez, J. C.
AU - Wang, Haichao
AU - Ochani, Mahendar
AU - Ochani, Kanta
AU - Yang, Huan
AU - Rabin, Aviva
AU - Leroith, Derek
AU - Lesniak, Maxine A.
AU - Böhm, Markus
AU - Maaser, Christian
AU - Kannengiesser, Klaus
AU - Donowitz, Mark
AU - Rabizadeh, Shervin
AU - Czura, Christopher J.
AU - Tracey, Kevin J.
AU - Westlake, Mark
AU - Zarfeshani, Aida
AU - Mehdi, Syed F.
AU - Danoff, Ann
AU - Ge, Xueliang
AU - Sanyal, Suparna
AU - Schwartz, Gary J.
AU - Roth, Jesse
N1 - Funding Information:
1Laboratory of Diabetes and Diabetes Related Research, US, USA; 2Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA; 3Hofstra Northwell School of Medicine, Hempstead, NY, USA; 4National Institutes of Health, Bethesda, Baltimore, MD, USA; 5Department of Emergency Medicine, Manhasset, NY, USA; 6Icahn School of Medicine at Mount Sinai, New York, NY, USA; 7University of Muenster, Münster, Germany; 8University Teaching Hospital, Luenburg, Germany; 9Johns Hopkins University School of Medicine, Baltimore, MD, USA; 10Cedars-Sinai Medical Center, Los Angeles, CA, USA; 11Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA; 12Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden and 13Albert Einstein College of Medicine, Bronx, NY, USA Correspondence: Jesse Roth (jesserothmd@hotmail.com) Xioaling Qiang, Anthony S. Liotta and Joseph Shiloach contributed equally to this work.
Funding Information:
The crucial funding for the work reported here was provided through the generous charitable contributions and shared vision of Alan and Tatyana Forman through Altronix Inc. and of the officers and trustees of the Russell Berrie Foundation, as well as the Feinstein Institute for Medical Research. We dedicate this paper to the memory of Dorothy T. Krieger MD (1927 –1985) a major contributors to the field of melanocortins, for her encouragement, contributions, and enthusiasm in the early stages of this work. We thank Domenico Accili, Rudolph L. Leibel (New York), Jeffrey I. Gordon, Ruth E. Ley, Fredrik Backhed, and their colleagues (St. Louis), Michael D. Walker and Yehiel Zick (Rehovot), Anna Catania (Milano), Jeffrey S. Flier, C. Ronald Kahn, Eleftheria Maratos-Flier (Boston), Cynthia Sears (Baltimore), Wolfram Domschke (Muenster), Andreas F. Pfeiffer (Potsdam), Jerrold Meinwald, Maureen A. Mackenzie, Astrid Shapiro, Christian Vaisse, and their colleagues (San Francisco), Pierre De Meyts (Copenhagen), and Simeon I. Taylor (Bethesda) for shared insights, helpful comments, and encouragement. For day to day support, we recognize the contributions of Arlene Riba, Barbara Lowell, Wilfred Erazo, Dee Prieto, and Kathleen Mcgill. Portions of the work were supported in part by the National Institutes of Health grants RO1-DK26523, RO1-DK61765, PO1-DK72084, and R24-DK64388 (The Hopkins Basic Research Digestive Diseases Development Core Center) to Mark Donowitz; RO-1-DK45496 to Cynthia L Sears; and 5-T32-HD4435 to Shervin Rabizadeh.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042174457&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042174457&partnerID=8YFLogxK
U2 - 10.1038/s41522-017-0039-9
DO - 10.1038/s41522-017-0039-9
M3 - Article
AN - SCOPUS:85042174457
SN - 2055-5008
VL - 3
JO - npj Biofilms and Microbiomes
JF - npj Biofilms and Microbiomes
IS - 1
M1 - 31
ER -