ROS-Mediated NLRP3 Inflammasome Activity Is Essential for Burn-Induced Acute Lung Injury

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2015 Nov 18

PMID 26576075

Citations 42

Authors

Shichao Han

Weixia Cai

Xuekang Yang

Yanhui Jia

Zhao Zheng

Hongtao Wang

Jun Li

Yan Li

Jianxin Gao

Lei Fan

Dahai Hu

Affiliations

Soon will be listed here.

Abstract

The NLRP3 inflammasome is necessary for initiating acute sterile inflammation. However, its role in the pathogenesis of burn-induced acute lung injury (ALI) is unknown. This study aimed to determine the role of the NLRP3 inflammasome and the signaling pathways involved in burn-induced ALI. We observed that the rat lungs exhibited enhanced inflammasome activity after burn, as evidenced by increased levels of NLRP3 expression and Caspase-1 activity and augmented inflammatory cytokines. Inhibition of NLRP3 inflammasome by BAY11-7082 attenuated burn-induced ALI, as demonstrated by the concomitant remission of histopathologic changes and the reduction of myeloperoxidase (MPO) activity, inflammatory cytokines in rat lung tissue, and protein concentrations in the bronchoalveolar lavage fluid (BALF). In the in vitro experiments, we used AMs (alveolar macrophages) challenged with burn serum to mimic the postburn microenvironment and noted that the serum significantly upregulated NLRP3 inflammasome signaling and reactive oxygen species (ROS) production. The use of ROS scavenger N-acetylcysteine (NAC) partially reversed NLRP3 inflammasome activity in cells exposed to burn serum. These results indicate that the NLRP3 inflammasome plays an essential role in burn-induced ALI and that burn-induced NLRP3 inflammasome activity is a partly ROS-dependent process. Targeting this axis may represent a promising therapeutic strategy for the treatment of burn-induced ALI.

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References

Rocha J, Eduardo-Figueira M, Barateiro A, Fernandes A, Brites D, Pinto R . Erythropoietin reduces acute lung injury and multiple organ failure/dysfunction associated to a scald-burn inflammatory injury in the rat. Inflammation. 2014; 38(1):312-26. DOI: 10.1007/s10753-014-0035-7. View

Yao X, Wigginton J, Maass D, Ma L, Carlson D, Wolf S . Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs. Am J Physiol Heart Circ Physiol. 2014; 306(6):H882-94. DOI: 10.1152/ajpheart.00475.2013. View

Liang X, Wang R, Wang F, Liu S, Guo F, Sun L . Sodium butyrate protects against severe burn-induced remote acute lung injury in rats. PLoS One. 2013; 8(7):e68786. PMC: 3708909. DOI: 10.1371/journal.pone.0068786. View

Zhang Y, Liu G, Dull R, Schwartz D, Hu G . Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation. Am J Physiol Lung Cell Mol Physiol. 2014; 307(2):L173-85. PMC: 4101793. DOI: 10.1152/ajplung.00083.2014. View

Wu J, Yan Z, Schwartz D, Yu J, Malik A, Hu G . Activation of NLRP3 inflammasome in alveolar macrophages contributes to mechanical stretch-induced lung inflammation and injury. J Immunol. 2013; 190(7):3590-9. PMC: 3608749. DOI: 10.4049/jimmunol.1200860. View

Youm Y, Kanneganti T, Vandanmagsar B, Zhu X, Ravussin A, Adijiang A . The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence. Cell Rep. 2012; 1(1):56-68. PMC: 3883512. DOI: 10.1016/j.celrep.2011.11.005. View

Diao L, Marshall A, Dai X, Bogdanovic E, Abdullahi A, Amini-Nik S . Burn plus lipopolysaccharide augments endoplasmic reticulum stress and NLRP3 inflammasome activation and reduces PGC-1α in liver. Shock. 2014; 41(2):138-44. PMC: 4635464. DOI: 10.1097/SHK.0000000000000075. View

Keyel P . How is inflammation initiated? Individual influences of IL-1, IL-18 and HMGB1. Cytokine. 2014; 69(1):136-45. DOI: 10.1016/j.cyto.2014.03.007. View

Turnage R, Nwariaku F, Murphy J, Schulman C, Wright K, Yin H . Mechanisms of pulmonary microvascular dysfunction during severe burn injury. World J Surg. 2002; 26(7):848-53. DOI: 10.1007/s00268-002-4063-3. View

10.

Ipaktchi K, Mattar A, Niederbichler A, Hoesel L, Vollmannshauser S, Hemmila M . Attenuating burn wound inflammatory signaling reduces systemic inflammation and acute lung injury. J Immunol. 2006; 177(11):8065-71. DOI: 10.4049/jimmunol.177.11.8065. View

11.

Enkhbaatar P, Wang J, Saunders F, Lange M, Hamahata A, Rehberg S . Mechanistic aspects of inducible nitric oxide synthase-induced lung injury in burn trauma. Burns. 2011; 37(4):638-45. PMC: 3936245. DOI: 10.1016/j.burns.2010.12.011. View

12.

Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer A . Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A. 2012; 109(28):11282-7. PMC: 3396518. DOI: 10.1073/pnas.1117765109. View

13.

Vergadi E, Vaporidi K, Theodorakis E, Doxaki C, Lagoudaki E, Ieronymaki E . Akt2 deficiency protects from acute lung injury via alternative macrophage activation and miR-146a induction in mice. J Immunol. 2013; 192(1):394-406. DOI: 10.4049/jimmunol.1300959. View

14.

Stanojcic M, Chen P, Harrison R, Wang V, Antonyshyn J, Zuniga-Pflucker J . Leukocyte infiltration and activation of the NLRP3 inflammasome in white adipose tissue following thermal injury. Crit Care Med. 2014; 42(6):1357-64. PMC: 4166573. DOI: 10.1097/CCM.0000000000000209. View

15.

Zhang J, Ying X, Liang W, Luo Z, Yang Z, Huang Y . Apoptosis in cardiac myocytes during the early stage after severe burn. J Trauma. 2008; 65(2):401-8. DOI: 10.1097/TA.0b013e31817cf732. View

16.

Ganter M, Roux J, Miyazawa B, Howard M, Frank J, Su G . Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms. Circ Res. 2008; 102(7):804-12. PMC: 2739091. DOI: 10.1161/CIRCRESAHA.107.161067. View

17.

Tian K, Liu X, Xu J, Deng L, Wang G . Propofol inhibits burn injury-induced hyperpermeability through an apoptotic signal pathway in microvascular endothelial cells. Braz J Med Biol Res. 2015; 48(5):401-7. PMC: 4445662. DOI: 10.1590/1414-431X20144107. View

18.

Osuka A, Hanschen M, Stoecklein V, Lederer J . A protective role for inflammasome activation following injury. Shock. 2011; 37(1):47-55. PMC: 3241872. DOI: 10.1097/SHK.0b013e318234f7ff. View

19.

Shao W, Yeretssian G, Doiron K, Hussain S, Saleh M . The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock. J Biol Chem. 2007; 282(50):36321-9. DOI: 10.1074/jbc.M708182200. View

20.

Xiang M, Shi X, Li Y, Xu J, Yin L, Xiao G . Hemorrhagic shock activation of NLRP3 inflammasome in lung endothelial cells. J Immunol. 2011; 187(9):4809-17. PMC: 3197874. DOI: 10.4049/jimmunol.1102093. View