A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis.
The triggering receptor expressed on myeloid cells (TREM)-1 is a recently discovered receptor expressed on the surface of neutrophils and a subset of monocytes. Engagement of TREM-1 has been reported to trigger the synthesis of proinflammatory cytokines in the presence of microbial products. Previously, we have identified a soluble form of TREM-1 (sTREM-1) and observed significant levels in serum samples from septic shock patients but not controls. Here, we investigated its putative role in the modulation of inflammation during sepsis. We observed that sTREM-1 was secreted by monocytes activated in vitro by LPS and in the serum of animals involved in an experimental model of septic shock. Both in vitro and in vivo, a synthetic peptide mimicking a short highly conserved domain of sTREM-1 appeared to attenuate cytokine production by human monocytes and protect septic animals from hyper-responsiveness and death. This peptide seemed to be efficient not only in preventing but also in down-modulating the deleterious effects of proinflammatory cytokines. These data suggest that in vivo modulation of TREM-1 by sTREM peptide might be a suitable therapeutic tool for the treatment of sepsis.
Gibot
Sébastien
S
Réanimation Médicale, Hôpital Central, 29 avenue du Maréchal de Lattre de Tassigny, 54035 Nancy Cedex, France. s.gibot@chu-nancy.fr
Kolopp-Sarda
Marie-Nathalie
MN
Béné
Marie-C
MC
Bollaert
Pierre-Edouard
PE
Lozniewski
Alain
A
Mory
Françoise
F
Levy
Bruno
B
Faure
Gilbert C
GC
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D019446:Endotoxemia / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000097:blood / Q000502:physiology*; D018805:Sepsis / Q000276:immunology* / Q000628:therapy; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010446:Peptide Fragments; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1