Abstract
Critical polytrauma patients present a series of pathophysiological disturbances, biochemical and molecular dysfunction, which comprise to be the major cause of intensive care unit admission. In regard to molecular damage, there exists a series of factors, which all together contribute to the aggravation of the clinical status leading to increased mortality rate in these patients. One of the most important biochemical factors involved is the nuclear transcription factor B (NF-κB). Impaired NF-κB functioning is reflected on the clinical status of the patient through increased production of pro-inflammatory molecule, leading to multiple organ dysfunction syndrome. In addition to this, through microRNAs interactions, various pathophysiological as well as biochemical disturbances are produced, which altogether further reduce the patient’s survival rate. In this paper, we would like to present the modifications seen in the expression of NF-κB in critically polytraumatized patients with sepsis. In additions to this, we would like to discuss the correlation between the microRNAs and its further implications in clinical status of these patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abraham E (2000) NF-κB activation. Crit Care Med 28:N100–N104
Abraham E (2003) Nuclear factor-κB and its role in sepsis-associated organ failure. J Infect Dis 187:S364–S369. doi:10.1086/374750
Altavilla D, Saitta A, Guarini S et al (2001) Oxidative stress causes nuclear factor-κB activation in acute hypovolemic hemorrhagic shock. Free Radic Biol Med 30:1055–1066. doi:10.1016/S0891-5849(01)00492-0
Arnalich F, Garcia-Palomero E, Lopez J et al (2000) Predictive value of nuclear factor kappa B activity and plasma cytokine levels in patients with sepsis. Infect Immun 68:1942–1945
Bains M, Hall ED (2012) Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta Mol Basis Dis 1822:675–684. doi:10.1016/j.bbadis.2011.10.017
Bakula M, Milicevic G, Bakula M et al (2016) Kinetics of ischemia-modified albumin following exercise-induced myocardial ischemia. Clin Lab 62:2015
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297. doi:10.1016/S0092-8674(04)00045-5
Bethea JR, Castro M, Keane RW et al (1998) Traumatic spinal cord injury induces nuclear factor-kappaB activation. J Neurosci 18:3251–3260
Birbach A, Gold P, Binder BR et al (2002) Signaling molecules of the NF-κB pathway shuttle constitutively between cytoplasm and nucleus. J Biol Chem 277:10842–10851
Blackwell TS, Christman JW (1997) The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 17:3–9
Böhrer H, Qiu F, Zimmermann T et al (1997) Role of NFkappaB in the mortality of sepsis. J Clin Invest 100:972–985. doi:10.1172/JCI119648
Bonaventura A, Liberale L, El-dib NH et al (2016) Case report anemia due to inflammation in an anti-coagulated patient with blue rubber bleb nevus syndrome. Clin Lab. doi:10.7754/Clin.Lab.2015.150617
Bosmann M, Ward PA (2013) The inflammatory response in sepsis. Trends Immunol 34:129–136. doi:10.1016/j.it.2012.09.004
Boursier G, Avignon A, Kuster N et al (2016) Procalcitonin, an independent marker of abdominal fat accumulation in obese patients. Clin Lab. doi:10.7754/Clin.Lab.2015.150736
Burkhardt M, Nienaber U, Pizanis A et al (2012) Acute management and outcome of multiple trauma patients with pelvic disruptions. Crit Care 16:R163. doi:10.1186/cc11487
Charchaflieh J, Rushbrook J, Worah S, Zhang M (2015) Activated complement factors as disease markers for sepsis. Dis Mark. doi:10.1155/2015/382463
Chen J, Chen X, Lei Y et al (2011) Vascular protective potential of the total flavanol glycosides from Abacopteris penangiana via modulating nuclear transcription factor-κB signaling pathway and oxidative stress. J Ethnopharmacol 136:217–223. doi:10.1016/j.jep.2011.04.052
Cho S-Y, Choi J-H (2014) Biomarkers of sepsis. Infect Chemother 46:1–12. doi:10.3947/ic.2014.46.1.1
Daniel Trancă S, Laura Petrişor C, Hagău N (2014) Biomarkers in polytrauma induced systemic inflammatory response syndrome and sepsis—a narrative review. Rom J Anaesth Intens Care 21:118–122
Dumache R, Rogobete AF, Bedreag OH et al (2015) Use of miRNAs as biomarkers in sepsis. Anal Cell Path. doi:10.1155/2015/186716
Etheridge A, Lee I, Hood L et al (2011) Extracellular microRNA: a new source of biomarkers. Mutat Res Fundam Mol Mech Mutagen 717:85–90. doi:10.1016/j.mrfmmm.2011.03.004
Garcia-alvarez M, Marik P, Bellomo R (2014) Sepsis-associated hyperlactatemia. Crit Care 18:503
Goodwin AJ, Guo C, Cook JA et al (2015) Plasma levels of microRNA are altered with the development of shock in human sepsis: an observational study. Crit Care 19:440. doi:10.1186/s13054-015-1162-8
Hafizi M, Atashi A, Bakhshandeh B et al (2012) MicroRNAs as markers for neurally committed CD133+/CD34+ stem cells derived from human umbilical cord blood. Biochem Genet 51:175–188. doi:10.1007/s10528-012-9553-x
Hayashi K, Tabe Y, Miida T (2016) Impact of clotting condition on the measurement of circulating microRNAs in serum. Clin Lab 1–5:2015. doi:10.7754/Clin.Lab.2015.150711
Hazeldine J, Hampson P, Lord JM (2014) The impact of trauma on neutrophil function. Injury 45:1824–1833. doi:10.1016/j.injury.2014.06.021
Huber-Lang M, Kovtun A, Ignatius A (2013) The role of complement in trauma and fracture healing. Semin Immunol 25:73–78. doi:10.1016/j.smim.2013.05.006
Hulsmans M, De Keyzer D, Holvoet P (2011) MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis. FASEB J 25:2515–2527. doi:10.1096/fj.11-181149
Hur W, Lee JH, Kim SW et al (2015) Downregulation of microRNA-451 in non-alcoholic steatohepatitis inhibits fatty acid-induced proinflammatory cytokine production through the AMPK/AKT pathway. Int J Biochem Cell Biol 64:265–276. doi:10.1016/j.biocel.2015.04.016
Kaya M, Yildiz MA (2008) Genetic diversity among Turkish native chickens, Denizli and Gerze, estimated by microsatellite markers. Biochem Genet 46:480–491. doi:10.1007/s10528-008-9164-8
Larche J, Lancel S, Hassoun SM et al (2006) Inhibition of mitochondrial permeability transition prevents sepsis-induced myocardial dysfunction and mortality. J Am Coll Cardiol 48:377–385. doi:10.1016/j.jacc.2006.02.069
Lenkala D, Gamazon ER, LaCroix B et al (2015) MicroRNA biogenesis and cellular proliferation. Transl Res. doi:10.1016/j.trsl.2015.01.012
Li J, Li N, Gu Y et al (2011) Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain. Chinese J Traumatol 14:354–358. doi:10.3760/cma.j.issn.1008-1275.2011.06.006
Li Y, Dalli J, Chiang N et al (2013) Plasticity of leukocytic exudates in resolving acute inflammation is regulated by MicroRNA and proresolving mediators. Immunity 39:885–898. doi:10.1016/j.immuni.2013.10.011
Libermann TA, Baltimore D (1990) Activation of interleukin-6 gene expression through the NF-kappaB transcription factor. Mol Cell Biol 10:2327–2334. doi:10.1128/MCB.10.5.2327.Updated
Liu SF, Malik AB (2006) NF-kappaB activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol 290:L622–L645. doi:10.1152/ajplung.00477.2005
Lu Q, Duan H, Yu J et al (2016) Are global coagulation and platelet parameters useful markers for predicting late-onset neonatal sepsis? Clin Lab. doi:10.7754/Clin.Lab.2015.150524
Luan Y, Yao Y, Xiao X, Sheng Z (2015) Insights into the apoptotic death of immune cells in sepsis. J Interferon Cytokine Res 35:17–22. doi:10.1089/jir.2014.0069
Ma X, Becker Buscaglia LE, Barker JR, Li Y (2011) MicroRNAs in NF-kappaB signaling. J Mol Cell Biol 3:159–166. doi:10.1093/jmcb/mjr007
Ma Y, Vilanova D, Atalar K et al (2013) Genome-wide sequencing of cellular microRNAs identifies a combinatorial expression signature diagnostic of sepsis. PLoS One 8:e75918. doi:10.1371/journal.pone.0075918
Macias S, Michlewski G, Cáceres JF (2009) Hormonal regulation of microRNA biogenesis. Mol Cell 36:172–173. doi:10.1016/j.molcel.2009.10.006
McGhan LJ, Jaroszewski DE (2012) The role of toll-like receptor-4 in the development of multi-organ failure following traumatic haemorrhagic shock and resuscitation. Injury 43:129–136. doi:10.1016/j.injury.2011.05.032
Mendes Arent A, De Souza LF, Walz R, Dafre AL (2014) Perspectives on molecular biomarkers of oxidative stress and antioxidant strategies in traumatic brain injury. Biomed Res Int. doi:10.1155/2014/723060
Ogbozor UD, Opene M, Renteria LS et al (2015) Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation. Mol Genet Metab Rep 4:11–18. doi:10.1016/j.ymgmr.2015.05.003
Olarerin-George AO, Anton L, Hwang Y-C et al (2013) A functional genomics screen for microRNA regulators of NF-kappaB signaling. BMC Biol 11:19. doi:10.1186/1741-7007-11-19
Rać ME, Suchy J, Kurzawski G et al (2012) Polymorphism of the CD36 gene and cardiovascular risk factors in patients with coronary artery disease manifested at a young age. Biochem Genet 50:103–111. doi:10.1007/s10528-011-9475-z
Ranji N, Sadeghizadeh M, Karimipoor M et al (2015) MicroRNAs signature in IL-2-induced CD4+ T cells and their potential targets. Biochem Genet 53:169–183. doi:10.1007/s10528-015-9677-x
Roderburg C, Luedde M, Vargas Cardenas D et al (2013) Circulating microRNA-150 serum levels predict survival in patients with critical illness and sepsis. PLoS One. doi:10.1371/journal.pone.0054612
Sagor MAT, Tabassum N, Potol MA, Alam MA (2015) Xanthine oxidase inhibitor, allopurinol, prevented oxidative stress, fibrosis, and myocardial damage in isoproterenol induced aged rats. Oxid Med Cell Longev. doi:10.1155/2015/478039
Schwartz MD, Moore EE, Moore FA et al (1996) Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med 24:1285–1292
Senol Tuncay S, Okyay P, Bardakci F (2009) Identification of NF-κB1 and NF-κBIΑ polymorphisms using PCR–RFLP assay in a Turkish population. Biochem Genet 48:104–112. doi:10.1007/s10528-009-9302-y
Shrivastava AK, Singh HV, Raizada A, Singh SK (2015) C-reactive protein, inflammation and coronary heart disease. Egypt Hear J 67:89–97. doi:10.1016/j.ehj.2014.11.005
Sies H (2015) Oxidative stress: a concept in redox biology and medicine. Redox Biol 4:180–183. doi:10.1016/j.redox.2015.01.002
Singer M (2014) The role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence 5:66–72. doi:10.4161/viru.26907
Staal FJ, Roederer M, Herzenberg LA (1990) Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. Proc Natl Acad Sci USA 87:9943–9947
Sun X, Icli B, Wara AK et al (2012) MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J Clin Invest 122:1–18. doi:10.1172/JCI61495DS1
Surbatovic M, Veljovic M, Jevdjic J et al (2013) Immunoinflammatory response in critically ill patients: severe sepsis and/or trauma. Mediat Inflamm. doi:10.1155/2013/362793
Tacke F, Roderburg C, Benz F et al (2014) Levels of circulating miR-133a are elevated in sepsis and predict mortality in critically ill patients. Crit Care Med 42:1096–1104. doi:10.1097/CCM.0000000000000131
Taganov KD, Boldin MP, Chang K-J, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486. doi:10.1073/pnas.0605298103
Tak PP, Firestein GS, Tak PP, Firestein GS (2001) NF-kappaB: a key role in inflammatory diseases. J Clin Invest 107:7–11. doi:10.1172/JCI11830
Thair SA, Walley KR, Nakada T-A et al (2011) A single nucleotide polymorphism in NF-{kappa}b inducing kinase is associated with mortality in septic shock. J Immunol 186:2321–2328. doi:10.4049/jimmunol.1002864
Wu M, Gu JT, Yi BIN et al (2015) microRNA-23b regulates the expression of inflammatory factors in vascular endothelial cells during sepsis. Exp Ther Med 9:1125–1132. doi:10.3892/etm.2015.2224
Acknowledgments
The authors would like to extend their thanks to County Emergency Hospital “Pius Brinzeu” Timisoara, and to the University of Medicine and Pharmacy “Victor Babes” Timisoara for their overwhelming support for conducting this study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interests
The authors have no conflict of interests to declare.
Rights and permissions
About this article
Cite this article
Papurica, M., Rogobete, A.F., Sandesc, D. et al. The Expression of Nuclear Transcription Factor Kappa B (NF-κB) in the Case of Critically Ill Polytrauma Patients with Sepsis and Its Interactions with microRNAs. Biochem Genet 54, 337–347 (2016). https://doi.org/10.1007/s10528-016-9727-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-016-9727-z