Triggering receptor expressed on myeloid cells 1 (TREM-1) is a protein that in humans is encoded by the TREM1gene.[5][6][7] TREM-1 is a surface receptor that amplifies inflammatory processes in vitro.
Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1), Fc receptors, CD14, Toll-like receptors (TLRs; e.g., TLR4), and cytokine receptors. TREM-1 amplifies toll-like receptors induced inflammation by further increasing the production of proinflammatory cytokines.[8] The ligand of TREM-1 is unknown, however, bacterial infection, ischemic stroke and challenge with lipopolysaccharide or lipoteichoic acid were observed to increase TREM-1 expression.[9] In granulocyte cells, C/EBPε was also shown to induce TREM-1 expression independently from inflammatory response.[10]
Interpreted from laboratory studies, TREM-1 may have a role in development of atherosclerosis,[11] non-alcoholic fatty liver disease,[12] and ischemic stroke.[13]
Soluble TREM-1[]
During inflammation, a soluble form of the molecule (sTREM-1) accumulates in the circulation, that is used as a biomarker to indicate inflammation. It is a matter of debate whether sTREM-1 is produced as a splice variant or as the results of proteolytic cleavage, but studies found evidence for both mechanisms.[14][15] sTREM-1 acts as a decoy receptor by competing for the unknown TREM-1 ligand. Therefore it provides a negative feedback loop for TREM-1 activation.[16] sTREM-1 has been demonstrated to provide valuable information about the extent of inflammatory processes and/or outcomes in the context of pneumonia,[17] sepsis,[18] inflammatory bowel disease[19][20] and liver cirrhosis.[21]
Model organisms[]
Model organisms have been used in the study of TREM1 function. A conditional knockout mouse line called Trem1tm1(KOMP)Vlcg was generated at the Wellcome Trust Sanger Institute.[22] Male and female animals underwent a standardized phenotypic screen[23] to determine the effects of deletion.[24][25][26][27] Additional screens performed: - In-depth immunological phenotyping[28]
^Bouchon A, Facchetti F, Weigand MA, Colonna M (April 2001). "TREM-1 amplifies inflammation and is a crucial mediator of septic shock". Nature. 410 (6832): 1103–7. doi:10.1038/35074114. PMID11323674.
^Tejera A, Santolaria F, Diez ML, Alemán-Valls MR, González-Reimers E, Martínez-Riera A, Milena-Abril A (June 2007). "Prognosis of community acquired pneumonia (CAP): value of triggering receptor expressed on myeloid cells-1 (TREM-1) and other mediators of the inflammatory response". Cytokine. 38 (3): 117–23. doi:10.1016/j.cyto.2007.05.002. PMID17659879.
^Tejera A, Santolaria F, Diez ML, Alemán-Valls MR, González-Reimers E, Martínez-Riera A, Milena-Abril A (June 2007). "Prognosis of community acquired pneumonia (CAP): value of triggering receptor expressed on myeloid cells-1 (TREM-1) and other mediators of the inflammatory response". Cytokine. 38 (3): 117–23. doi:10.1016/j.cyto.2007.05.002. PMID17659879.
^Park JJ, Cheon JH, Kim BY, Kim DH, Kim ES, Kim TI, et al. (July 2009). "Correlation of serum-soluble triggering receptor expressed on myeloid cells-1 with clinical disease activity in inflammatory bowel disease". Digestive Diseases and Sciences. 54 (7): 1525–31. doi:10.1007/s10620-008-0514-5. PMID18975078.
^Jung YS, Park JJ, Kim SW, Hong SP, Kim TI, Kim WH, Cheon JH (November 2012). "Correlation between soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) expression and endoscopic activity in inflammatory bowel diseases". Digestive and Liver Disease. 44 (11): 897–903. doi:10.1016/j.dld.2012.05.011. PMID22721842.
^Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID85911512.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Bouchon A, Facchetti F, Weigand MA, Colonna M (April 2001). "TREM-1 amplifies inflammation and is a crucial mediator of septic shock". Nature. 410 (6832): 1103–7. Bibcode:2001Natur.410.1103B. doi:10.1038/35074114. PMID11323674. S2CID4403589.
Kelker MS, Foss TR, Peti W, Teyton L, Kelly JW, Wüthrich K, Wilson IA (September 2004). "Crystal structure of human triggering receptor expressed on myeloid cells 1 (TREM-1) at 1.47 A". Journal of Molecular Biology. 342 (4): 1237–48. doi:10.1016/j.jmb.2004.07.089. PMID15351648.
Plachouras D, Routsi C, Giamarellos-Bourboulis EJ, Spyridaki E, Andrianakis I, Metzelopoulos S, et al. (2006). "Monocytes as a site of production of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the septic host". Scandinavian Journal of Infectious Diseases. 38 (10): 909–15. doi:10.1080/00365540600786523. PMID17008237. S2CID7754570.
