Received March 23, 2016; Accepted July 28, 2016; Published September 09, 2016
http://dx.doi.org/10.18081/2333-5106/016-301-313
Juan J Arcaroli; Daniel H Relja; Panagiotis Breed; Georgios K Chou; Andrew Morin; David B. Greig
Abstract
Burn injury often leads to serious lung injuries, resulting in respiratory dysfunction that can lead to a higher morbidity and mortality. In an effort to improve the life quality of those afflicted, it is essential to understand the underlying mechanisms of lung injury caused by burn trauma. Burn injury can lead to pulmonary inflammation and progressive edema, which is a direct consequence of systemic inflammatory response syndrome (SIRS) or acute respiratory distress syndrome (ARDS). In the case of burn injuries, the inflammatory response becomes systemic, which causes injuries to multiple organ systems, especially the lung. There are many inflammatory mediators, such as interleukins and protein factors, which are released from the burned tissue. These mediators activate the nuclear factor-kappaB (NF-κB) pathway to promote the expression of inflammatory cytokines, lung epithelium injury chemokines, and adhesion factors, leading to inflammatory cell activation and lung tissue injury. 17β-estradiol, an endogenous female sex hormone, has been shown to exert a protective effect in a number of diseases. 17β-estradiol downregulates the activation of NF-κB by inhibiting the degradation of inhibitor of κB (IκB), thereby preventing the expression of proinflammatory cytokines and chemokines. 17β-estradiol also limits the formation of reactive oxygen species, thereby inhibiting the activation of NF-κB. 17β-estradiol diminishes the release of proinflammatory mediators, leading to a hepatoprotective effect against systemic inflammatory responses. However, it is unclear whether this compound can protect lungs from burn-induced injury and inflammation. The aim of the current investigation was to explore the time course of lung injury and inflammation following burn trauma in rats, with particular emphasis on the role played by NF-κB, and to investigate the protective effects and mechanisms of 17β-estradiol in lung injury and inflammation following burn trauma.
Keyword: Acute lung injury; 17β-estradiol; NF-κB; Proinflammatory cytokine
References
1. Zaets SB, Xu DZ, Lu Q, Feketova E, Berezina TL, Gruda M, Malinina IV, Deitch EA, Olsen EH: Recombinant factor XIII diminishes multiple organ dysfunction in rats caused by gut ischemia-reperfusion injury Shock 2009;31(6):621-626. [PubMed]
2. Brusselaers N, Monstrey S, Vogelaers D, Hoste E, Blot. Severe burn injury in Europe: a systematic review of the incidence, etiology, morbidity, and mortality. Crit Care 2010;14 (5) R188. [PubMed]
3. Schultz C; Morin A; Greig DB. IL-37/IL-18Rα complex: receptors, signaling and pathogenesis of diseases. American Journal of BioMedicine 2014;2:48–56. [Abstract/Full-Text]
4. Koo DJ, Chaudry IH, Wang P. Kupffer cells are responsible for producing inflammatory cytokines and hepatocellular dysfunction during early sepsis. J Surg Res 1999; 83(2) 151–157. [PubMed]
5. Barnes KC. Genetic determinants and ethnic disparities in sepsis-associated acute lung injury. Proc Am Thorac Soc 2005; 2:195–201. [PubMed]
6. Arcaroli JJ, Hokanson JE, Abraham E, Geraci M, Murphy JR, et al. Extracellular superoxide dismutase haplotypes are associated with acute lung injury and mortality. Am J Respir Crit Care Med 2009;179: 105–112. [PubMed]
7. Marzec JM, Christie JD, Reddy SP, Jedlicka AE, Vuong H, et al. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J 2007;21: 2237–2246. [PubMed]
8. Bernard GR, Reines HD, Brigham KL, Carlet J, Flake J, et al.The American European consensus conference on ARDS: definitions, mechanisma, relevant outcomes and clinical trials coordination. Am J Resp Crit Care Med 1994;149: 818–824. [PubMed]
9. Suzuki M, Tachibana I, Takeda Y, He P, Minami S, et al. Tetraspanin CD9 negatively regulates lipopolysaccharide-induced macrophage activation and lung inflammation. J Immunol 2009;182: 6485–6493. [PubMed]
10. Christie JD, Ma SF, Aplenc R, Li M, Lanken PN, et al. Variation in the myosin light chain kinase gene is associated with development of acute lung injury after major trauma. Crit Care Med 2008;36: 2794–2800. [PubMed]
11. Crosby LM, Waters CM. Epithelial repair mechanisms in the lung. Am J Physiol Lung Cell Mol Physiol 2010;298: L715–731. [PubMed]
12. Barnes KC. Genetic determinants and ethnic disparities in sepsis-associated acute lung injury. Proceedings of the American Thoracic Society 2005; 2:195–201. [PubMed]
13. Wurfel MM, Gordon AC, Holden TD, Radella F, Strout J, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am J Respir Crit Care Med 2008;178: 710–720.
14. Healthcare Disparities in Patients with Acute Respiratory Distress Syndrome. Toward Equity. American Journal of Respiratory and Critical Care Medicine 2013;188:6, 631-632. [Abstract/Full-Text]
15. Respiratory Infection and the Impact of Pulmonary Immunity on Lung Health and Disease. American Journal of Respiratory and Critical Care Medicine 2012;186(9):824-829. [Abstract/Full-Text]
16. ANGPT2 Genetic Variant Is Associated with Trauma-associated Acute Lung Injury and Altered Plasma Angiopoietin-2 Isoform Ratio. American Journal of Respiratory and Critical Care Medicine 2011;183(10)1344-1353. [Abstract/Full-Text]
17. Extracellular Superoxide Dismutase Haplotypes and Acute Lung Injury. American Journal of Respiratory and Critical Care Medicine 2009;179:89-91. [Abstract/Full-Text]
18. Wurfel MM, Gordon AC, Holden TD, Radella F, Strout J, Kajikawa O, Ruzinski JT, Rona G, Black RA, Stratton S, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am J Respir Crit Care Med 2008;178:710–720. [PubMed]
19. Christie JD, Ma SF, Aplenc R, Li M, Lanken PN, Shah CV, Fuchs B, Albelda SM, Flores C, Garcia JG. Variation in the MYLK gene is associated with development of acute lung injury after major trauma. Crit Care Med 2008;36:2794–2800. [PubMed]
20. McVean GA, Myers SR, Hunt S, Deloukas P, Bentley DR, Donnelly P. The fine-scale structure of recombination rate variation in the human genome. Science 2004;304:581–584. [PubMed]
21. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354:2564–2575. [PubMed]
22. IL1RN Coding Variant Is Associated with Lower Risk of Acute Respiratory Distress Syndrome and Increased Plasma IL-1 Receptor Antagonist. American Journal of Respiratory and Critical Care Medicine 2103;187:950-959. [Abstract/Full-Text]
23. Type 2 Deiodinase and Host Responses of Sepsis and Acute Lung Injury. American Journal of Respiratory Cell and Molecular Biology 2011;45:1203-1211. [Abstract/Full-Text]
24. Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med 1995;151:293–301. [PubMed]
25. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 1999;282:54–61. [PubMed]
26. Meyer NJ, Huang Y, Singleton PA, Sammani S, Moitra J, Evenoski CL, Husain AN, Mitra S, Moreno-Vinasco L, Jacobson JR, et al. GADD45a is a novel candidate gene in inflammatory lung injury via influences on Akt signaling. FASEB J 2009;23:1325–1337. [PubMed]
