Abstract
The triggering receptor expressed by myeloid cells-1 (TREM-1) plays an important role in infectious and autoimmune diseases but how it contributes to ventilation-induced lung injury (VILI) and inflammation is unclear. Here, we examine the possibility that TREM-1 activates signaling dependent on Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and nuclear factor (NF)-κB, which leads in turn to VILI. In a mouse model of VILI, which we validated based on lung edema and histopathology as well as cytokine levels, we examine mRNA and protein levels of TREM-1, TLR4, MyD88, NF-κB and its inhibitory protein I-κB in animals subjected to ventilation at normal or high tidal volume. The extent of lung edema, injury and inflammation were higher in the high tidal volume animals, as were the expression levels of all proteins examined. Treatment with TREM-1 agonist aggravated these effects, whereas treatment with TREM-1 antagonist attenuated them. Our results suggest that aggravation of VILI by TREM-1 in mice may be associated with TLR4-MyD88-NF-κB-dependent signaling.
Similar content being viewed by others
Abbreviations
- TREM-1:
-
Triggering receptor expressed by myeloid cells-1
- VILI:
-
Ventilation-induced lung injury
- TLR4:
-
Toll-like receptor 4
- MyD88:
-
Myeloid differentiation factor 88
- NF-κB:
-
Nuclear factor-κB
- I-κB:
-
Nuclear factor-κB and its inhibitory protein
- IL-1β:
-
Interleukin (IL)-1β
- TNF-α:
-
Tumor necrosis factor-α
- MV:
-
Mechanical ventilation
- VT:
-
Tidal volume
- HTV:
-
High tidal volume
- BALF:
-
Bronchoalveolar lavage fluid
- W/D:
-
Wet/dry ratio
- RT-qPCR:
-
Real-time qualitative polymerase chain reaction
References
Arslantas MK, Kara HV, Tuncer BB, Yildizeli B, Yuksel M, Bostanci K, Bekiroglu N, Kararmaz A, Cinel I, Batirel HF (2015) Effect of the amount of intraoperative fluid administration on postoperative pulmonary complications following anatomic lung resections. J Thorac Cardiovasc Surg 149:314–320 321.e311
Arts RJ, Joosten LA, Dinarello CA, Kullberg BJ, van der Meer JW, Netea MG (2011) TREM-1 interaction with the LPS/TLR4 receptor complex. Eur Cytokine Netw 22:11–14
Barnes PJ, Karin M (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071
Beitler JR, Malhotra A, Thompson BT (2016) Ventilator-induced lung injury. Clin Chest Med 37:633–646
Bouchon A, Dietrich J, Colonna M (2000) Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 164:4991–4995
Camp SM, Ceco E, Evenoski CL, Danilov SM, Zhou T, Chiang ET, Moreno-Vinasco L, Mapes B, Zhao J, Gursoy G, Brown ME, Adyshev DM, Siddiqui SS, Quijada H, Sammani S, Letsiou E, Saadat L, Yousef M, Wang T, Liang J, Garcia JG (2015) Unique toll-like receptor 4 activation by NAMPT/PBEF induces NFkappaB signaling and inflammatory lung injury. Sci Rep 5:13135
Campanholle G, Mittelsteadt K, Nakagawa S, Kobayashi A, Lin SL, Gharib SA, Heinecke JW, Hamerman JA, Altemeier WA, Duffield JS (2013) TLR-2/TLR-4 TREM-1 signaling pathway is dispensable in inflammatory myeloid cells during sterile kidney injury. PLoS One 8:e68640
Cressoni M, Gotti M, Chiurazzi C, Massari D, Algieri I, Amini M, Cammaroto A, Brioni M, Montaruli C, Nikolla K, Guanziroli M, Dondossola D, Gatti S, Valerio V, Vergani GL, Pugni P, Cadringher P, Gagliano N, Gattinoni L (2016) Mechanical power and development of ventilator-induced lung injury. Anesthesiology 124:1100–1108
Dai H, Pan L, Lin F, Ge W, Li W, He S (2015) Mechanical ventilation modulates toll-like receptors 2, 4, and 9 on alveolar macrophages in a ventilator-induced lung injury model. J Thorac Dis 7:616–624
Determann RM, Millo JL, Gibot S, Korevaar JC, Vroom MB, van der Poll T, Garrard CS, Schultz MJ (2005) Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia. Intensive Care Med 31:1495–1500
Dong L, Zhou Y, Zhu ZQ, Liu T, Duan JX, Zhang J, Li P, Hammcok BD, Guan CX (2017) Soluble epoxide hydrolase inhibitor suppresses the expression of triggering receptor expressed on myeloid Cells-1 by inhibiting NF-kB activation in murine macrophage. Inflammation 40:13–20
Gao S, Yuan L, Wang Y, Hua C (2017) Enhanced expression of TREM-1 in splenic cDCs in lupus prone mice and it was modulated by miRNA-150. Mol Immunol 81:127–134
Gibot S, Massin F, Alauzet C, Montemont C, Lozniewski A, Bollaert PE, Levy B (2008) Effects of the TREM-1 pathway modulation during mesenteric ischemia-reperfusion in rats. Crit Care Med 36:504–510
Grover V, Pantelidis P, Soni N, Takata M, Shah PL, Wells AU, Henderson DC, Kelleher P, Singh S (2014) A biomarker panel (Bioscore) incorporating monocytic surface and soluble TREM-1 has high discriminative value for ventilator-associated pneumonia: a prospective observational study. PLoS One 9:e109686
Huang C, Pan L, Lin F, Dai H, Fu R (2017) Monoclonal antibody against Toll-like receptor 4 attenuates ventilator-induced lung injury in rats by inhibiting MyD88- and NF-kappaB-dependent signaling. Int J Mol Med 39:693–700
Lai RP, Meintjes G, Wilkinson KA, Graham CM, Marais S, Van der Plas H, Deffur A, Schutz C, Bloom C, Munagala I, Anguiano E, Goliath R, Maartens G, Banchereau J, Chaussabel D, O'Garra A, Wilkinson RJ (2015) HIV-tuberculosis-associated immune reconstitution inflammatory syndrome is characterized by Toll-like receptor and inflammasome signalling. Nat Commun 6:8451
Lanier LL (2008) Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol 9:495–502
Li H, Su X, Yan X, Wasserloos K, Chao W, Kaynar AM, Liu ZQ, Leikauf GD, Pitt BR, Zhang LM (2010) Toll-like receptor 4-myeloid differentiation factor 88 signaling contributes to ventilator-induced lung injury in mice. Anesthesiology 113:619–629
Liu T, Zhou Y, Li P, Duan JX, Liu YP, Sun GY, Wan L, Dong L, Fang X, Jiang JX, Guan CX (2016) Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation. Sci Rep 6:39473
Müller HC, Hellwig K, Rosseau S, Tschernig T, Schmiedl A, Gutbier B, Schmeck B, Hippenstiel S, Peters H, Morawietz L (2010) Simvastatin attenuates ventilator-induced lung injury in mice. Crit Care 14:R143
Murakami Y, Kohsaka H, Kitasato H, Akahoshi T (2007) Lipopolysaccharide-induced up-regulation of triggering receptor expressed on myeloid cells-1 expression on macrophages is regulated by endogenous prostaglandin E2. J Immunol 178:1144–1150
Palazzo SJ, Simpson TA, Simmons JM, Schnapp LM (2012) Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as a diagnostic marker of ventilator-associated pneumonia. Respir Care 57:2052–2058
Pandupuspitasari NS, Khan FA, Huang CJ, Chen X, Zhang S (2016) Novel attributions of TREMs in immunity. Curr Issues Mol Biol 20:47–54
Park MS, He Q, Edwards MG, Sergew A, Riches DW, Albert RK, Douglas IS (2012) Mitogen-activated protein kinase phosphatase-1 modulates regional effects of injurious mechanical ventilation in rodent lungs. Am J Respir Crit Care Med 186:72–81
Slutsky AS, Ranieri VM (2013) Ventilator-induced lung injury. N Engl J Med 369:2126–2136
Thankam FG, Dilisio MF, Dougherty KA, Dietz NE, Agrawal DK (2016) Triggering receptor expressed on myeloid cells and 5'adenosine monophosphate-activated protein kinase in the inflammatory response: a potential therapeutic target. Expert Rev Clin Immunol 12:1239–1249
Vieillard-Baron A, Dreyfuss D (2017) Ventilator-induced lung injury: follow the right direction! Another piece of the puzzle in the VILI epic. Am J Respir Crit Care Med 196:1366–1368
Wu GJ, Chen TL, Ueng YF, Chen RM (2008) Ketamine inhibits tumor necrosis factor-alpha and interleukin-6 gene expressions in lipopolysaccharide-stimulated macrophages through suppression of toll-like receptor 4-mediated c-Jun N-terminal kinase phosphorylation and activator protein-1 activation. Toxicol Appl Pharmacol 228:105–113
Yang P, Yang N, Zhang X, Xu X (2014) The significance and mechanism of propofol on treatment of ischemia reperfusion induced lung injury in rats. Cell Biochem Biophys 70:1527–1532
Zhang G, Liu H, Huang J, Chen S, Pan X, Huang H, Wang L (2016) TREM-1 low is a novel characteristic for tumor-associated macrophages in lung cancer. Oncotarget 7:40508–40517
Zheng H, Heiderscheidt CA, Joo M, Gao X, Knezevic N, Mehta D, Sadikot RT (2010) MYD88-dependent and -independent activation of TREM-1 via specific TLR ligands. Eur J Immunol 40:162–171
Zhou X, Wang Y, Wang Y, Cipriano P, Xiao B, Zhou W (2017) Inhibition of triggering receptor expressed on myeloid cells-1 ameliorates experimental autoimmune neuritis. Mol Med Rep 15:1565–1570
Zhu J, Duan G, Wang H, Cao M, Liu Y (2016) TREM-1 activation modulates dsRNA induced antiviral immunity with specific enhancement of MAPK signaling and the RLRs and TLRs on macrophages. Exp Cell Res 345:70–81
Author information
Authors and Affiliations
Contributions
Ji-feng Feng conceived and designed the experiments. Xiao-xia Wang and Bi-jun Luo performed the experiments, analyzed data and wrote the paper. Yan-yan Lu, Deng-ge Pang, Jian-qiu Zheng, Jian-lan Mo, Tao Chi, Hui Huang and Jiang-li Lan reviewed the study proposal and served as scientific advisor. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Wang, X., Luo, B., Lu, Y. et al. The triggering receptor expressed by myeloid cells-1 activates TLR4-MyD88-NF-κB-dependent signaling to aggravate ventilation-induced lung inflammation and injury in mice. Cell Tissue Res 374, 137–148 (2018). https://doi.org/10.1007/s00441-018-2853-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-018-2853-7