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

被引：19

作者：

Qiang, Xiaoling ^{[1
,2
,3
]}

Liotta, Anthony S. ^{[4
]}

Shiloach, Joseph ^{[4
]}

Gutierrez, J. C. ^{[4
]}

Wang, Haichao ^{[2
,5
]}

Ochani, Mahendar ^{[2
]}

Ochani, Kanta ^{[2
]}

Yang, Huan ^{[2
]}

Rabin, Aviva ^{[1
,2
]}

LeRoith, Derek ^{[6
]}

Lesniak, Maxine A. ^{[4
]}

Boehm, Markus ^{[7
]}

Maaser, Christian ^{[8
]}

Kannengiesser, Klaus ^{[8
]}

Donowitz, Mark ^{[9
]}

Rabizadeh, Shervin ^{[10
]}

Czura, Christopher J. ^{[2
,3
]}

Tracey, Kevin J. ^{[2
,3
]}

Westlake, Mark ^{[1
,2
]}

Zarfeshani, Aida ^{[1
,2
]}

Mehdi, Syed F. ^{[1
,2
]}

Danoff, Ann ^{[11
]}

Ge, Xueliang ^{[12
]}

Sanyal, Suparna ^{[12
]}

Schwartz, Gary J. ^{[13
]}

Roth, Jesse ^{[1
,2
,3
,13
]}

机构：

[1] US, Lab Diabet & Diabet Related Res, Manhasset, NY USA

[2] Northwell Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA

[3] Hofstra Northwell Sch Med, Hempstead, NY 11549 USA

[4] NIH, Baltimore, MD USA

[5] Dept Emergency Med, Manhasset, NY USA

[6] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[7] Univ Munster, Munster, Germany

[8] Univ Teaching Hosp, Luenburg, Germany

[9] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[10] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[11] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[12] Uppsala Univ, Dept Cell & Mol Biol, Uppsala, Sweden

[13] Albert Einstein Coll Med, Bronx, NY 10467 USA

来源：

NPJ BIOFILMS AND MICROBIOMES | 2017年 / 3卷

基金：

美国国家卫生研究院;

关键词：

SEPARATION; APOPTOSIS; RELEASE; SYSTEM; CELLS; FACES; HMGB1;

D O I：

10.1038/s41522-017-0039-9

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页数：11

共 41 条

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