Downregulation of high mobility group box 1 attenuates the severity of acute lung injury in endotoxemic mice

Zhang,Xiaojuan; Luan,Zhenggang; Liang,Yingjian; Liu,Yina; Ma,Xiaochun

doi:10.3892/mmr.2015.3251

Downregulation of high mobility group box 1 attenuates the severity of acute lung injury in endotoxemic mice

Authors:
- Xiaojuan Zhang
- Zhenggang Luan
- Yingjian Liang
- Yina Liu
- Xiaochun Ma
View Affiliations

Affiliations: Intensive Care Unit, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: January 26, 2015 https://doi.org/10.3892/mmr.2015.3251
Pages: 4513-4517

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

High mobility group box 1 (HMGB1) is a systemic inflammation‑associated cytokine mediator. The aim of the present study was to examine the effect of the downregulation of HMGB1 in a lipopolysaccharide (LPS)‑induced mouse model of acute lung injury (ALI). It was identified that serum levels of tumor necrosis factor‑α and interleukin‑1β, lung myeloperoxidase activity and malondialdehyde content, as well as lung wet/dry weight ratios were all increased following LPS challenge. However, LPS‑mediated increases in these parameters were significantly downregulated in HMGB1 small interfering (si)RNA‑treated mice versus the negative control siRNA‑treated mice. In addition, the administration of HMGB1 siRNA in LPS‑treated mice resulted in a decreased DNA binding activity of nuclear factor‑κB (NF‑κB) in the lung. It was demonstrated that downregulation of HMGB1 decreases inflammation and the severity of sepsis associated with ALI, possibly via inhibiting the NF‑κB DNA‑binding activity. The present data support HMGB1 as a contributor to the pathogenesis of LPS‑induced sepsis and ALI.

View Figures

View References

1	Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J and Pinsky MR: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 29:1303–1310. 2001. View Article : Google Scholar : PubMed/NCBI
2	Fry DE: Sepsis, systemic inflammatory response, and multiple organ dysfunction: the mystery continues. Am Surg. 78:1–8. 2012.PubMed/NCBI
3	Ware LB and Matthay MA: The acute respiratory distress syndrome. N Engl J Med. 342:1334–1349. 2000. View Article : Google Scholar : PubMed/NCBI
4	Matthay MA and Zemans RL: The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 6:147–163. 2011. View Article : Google Scholar :
5	Matthay MA and Zimmerman GA: Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol. 33:319–327. 2005. View Article : Google Scholar : PubMed/NCBI
6	Erickson SE, Martin GS, Davis JL, Matthay MA and Eisner MD; NIH NHLBI ARDS Network: Recent trends in acute lung injury mortality: 1996–2005. Crit Care Med. 37:1574–1579. 2009. View Article : Google Scholar : PubMed/NCBI
7	Zimmerman JJ, Akhtar SR, Caldwell E and Rubenfeld GD: Incidence and outcomes of pediatric acute lung injury. Pediatrics. 124:87–95. 2009. View Article : Google Scholar : PubMed/NCBI
8	Hudson LD, Milberg JA, Anardi D and Maunder RJ: Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 151:293–301. 1995. View Article : Google Scholar : PubMed/NCBI
9	Gando S: Microvascular thrombosis and multiple organ dysfunction Syndrome. Crit Care Med. 38(Suppl 2): S35–S42. 2010. View Article : Google Scholar : PubMed/NCBI
10	Levi M and van der Poll T: Inflammation and coagulation. Crit Care Med. 38(Suppl 2): S26–S34. 2010. View Article : Google Scholar : PubMed/NCBI
11	Andersson U, Wang H, Palmblad K, et al: High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 192:565–570. 2000. View Article : Google Scholar : PubMed/NCBI
12	Wang H, Bloom O, Zhang M, et al: HMG-1 as a late mediator of endotoxin lethality in mice. Science. 285:248–251. 1999. View Article : Google Scholar : PubMed/NCBI
13	Wang H, Yang H and Tracey KJ: Extracellular role of HMGB1 in inflammation and sepsis. J Intern Med. 255:320–331. 2004. View Article : Google Scholar : PubMed/NCBI
14	Fiuza C, Bustin M, Talwar S, et al: Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood. 101:2652–2660. 2003. View Article : Google Scholar
15	Mullins GE, Sunden-Cullberg J, Johansson AS, et al: Activation of human umbilical vein endothelial cells leads to relocation and release of high-mobility group box chromosomal protein 1. Scand J Immunol. 60:566–573. 2004. View Article : Google Scholar : PubMed/NCBI
16	Bae JS and Rezaie AR: Activated protein C inhibits high mobility group box 1 signaling in endothelial cells. Blood. 118:3952–3959. 2011. View Article : Google Scholar : PubMed/NCBI
17	Yasuda T, Ueda T, Takeyama Y, et al: Significant increase of serum high-mobility group box chromosomal protein 1 levels in patients with severe acute pancreatitis. Pancreas. 33:359–363. 2006. View Article : Google Scholar : PubMed/NCBI
18	Gibot S, Massin F, Cravoisy A, et al: High-mobility group box 1 protein plasma concentrations during septic shock. Intensive Care Med. 33:1347–1353. 2007. View Article : Google Scholar : PubMed/NCBI
19	Gaïni S, Pedersen SS, Koldkjaer OG, Pedersen C and Møller HJ: High mobility group box-1 protein in patients with suspected community-acquired infections and sepsis: a prospective study. Crit Care. 11:R322007. View Article : Google Scholar : PubMed/NCBI
20	van Zoelen MA, Laterre PF, van Veen SQ, et al: Systemic and local high mobility group box 1 concentrations during severe infection. Crit Care Med. 35:2799–2804. 2007. View Article : Google Scholar : PubMed/NCBI
21	Karlsson S, Pettilä V, Tenhunen J, Laru-Sompa R, Hynninen M and Ruokonen E: HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis. Intensive Care Med. 34:1046–1053. 2008. View Article : Google Scholar : PubMed/NCBI
22	Silva E, Arcaroli J, He Q, et al: HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury. Intensive Care Med. 33:1829–1839. 2007. View Article : Google Scholar : PubMed/NCBI
23	Zhang XJ, Luan ZG and Ma XC: shRNAs targeting high-mobility group box-1 inhibit E-selectin expression via homeobox A9 in human umbilical vein endothelial cells. Mol Med Rep. 7:1251–1256. 2013.PubMed/NCBI
24	Luan ZG, Zhang XJ, Yin XH, et al: Downregulation of HMGB1 protects against the development of acute lung injury after severe acute pancreatitis. Immunobiology. 218:1261–1270. 2013. View Article : Google Scholar : PubMed/NCBI
25	Cannon JG, Tompkins RG, Gelfand JA, et al: Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis. 161:79–84. 1990. View Article : Google Scholar : PubMed/NCBI
26	Minamino T and Komuro I: Regeneration of the endothelium as a novel therapeutic strategy for acute lung injury. J Clin Invest. 116:2316–2319. 2006. View Article : Google Scholar : PubMed/NCBI
27	Pahl HL: Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 18:6853–6866. 1999. View Article : Google Scholar : PubMed/NCBI
28	Rakonczay Z Jr, Hegyi P, Takács T, McCarroll J and Saluja AK: The role of NF-kappaB activation in the pathogenesis of acute pancreatitis. Gut. 57:259–267. 2008. View Article : Google Scholar