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.
Highlights
Every mammalian cell is a secretory cell, programed to release a limited menu of hormone-like molecules
In the present paper we introduce, a melanocortin-like peptide spontaneously released from Eschericia coli during growth in a simple medium (MECO-1 = melanocortin-like peptide of E. coli) that has structure and function in mammalian systems that is close to alphamelanonocyte-stimulating hormone and adrenocorticotropin (ACTH), the best studied melanocortin hormones of humans, mice, and other mammals.[7,8,9,10,11,12]
That the melanocortin-1 receptor (MC1R) melanocortin receptor is playing a significant role in controlling inflammation in the intestine in vivo is supported by the observations that mice null in MC1R are devastated by dextran-induced colitis.[24]
Summary
Every mammalian cell is a secretory cell, programed to release a limited menu of hormone-like molecules. Every mammalian cell displays a modest menu of cell surface receptors that recognize and respond to the hormone-like molecules in the extracellular medium. This whole body endocrine-like system provides exquisite coordination for the hundreds of trillions of cells that constitute the host. MECO-1 is at least as powerful as alpha-MSH in rescuing mice from death due to sterile (lipopolysaccharide (LPS)induced) sepsis and polymicrobial (cecal ligation-induced) sepsis These studies lead us to raise the possibility that microbes resident in the gut produce messenger molecules that can act on mammalian hosts via the hosts’ endogenous hormone signaling pathways to counter the pro-inflammatory stimuli of microbial components and to act much more broadly as a newly recognized endocrine-like organ. New melanocortin-like peptide of E. coli suppress X Qiang et al
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
