Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice

Yong Zhou, Tian Liu, Jia Xi Duan, Ping Li, Guo Ying Sun, Yong Ping Liu, Jun Zhang, Liang Dong, Kin Sing Stephen Lee, Bruce D. Hammock, Jian Xin Jiang, Cha Xiang Guan

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid with antihypertensive, profibrinolytic, and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols. The aim of this study was to investigate the role of sEH inhibitor trifluoromethoxyphenyl propionylpiperidin urea (TPPU) and EETs in lipopolysaccharide (LPS)-induced ALI of mice. Our studies revealed that inhibition of sEH with TPPU attenuated the morphological changes in mice, decreased the neutrophil infiltration to the lung, pro-inflammatory cytokine levels (IL-1β and TNF-α) in serum and bronchoalveolar lavage fluid (BALF), and alveolar capillary leakage (lung wet/dry ratio and total protein concentration in BALF). TPPU improved the survival rate of LPS-induced ALI. In addition, in vitro experiments revealed that both TPPU and EETs (11,12-EET and 14,15-EET) suppressed the expression of IL-1β and TNF-α, and LDH release in RAW264.7 cells. These results indicate that EETs play a role in dampening LPS-induced acute lung inflammation, and suggest that sEH could be a valuable candidate for the treatment of ALI.

Original languageEnglish (US)
Pages (from-to)638-645
Number of pages8
JournalShock
Volume47
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Epoxide Hydrolases
Acute Lung Injury
Lipopolysaccharides
Urea
Survival
Bronchoalveolar Lavage Fluid
Interleukin-1
Pneumonia
Cytokines
Lung
Neutrophil Infiltration
Vascular System Injuries
Pulmonary Edema
Unsaturated Fatty Acids
Cytochrome P-450 Enzyme System
Antihypertensive Agents
Edema
Neutrophils
Anti-Inflammatory Agents
Survival Rate

Keywords

  • Acute lung injury
  • epoxyeicosatrienoic acids
  • inflammation
  • lipopolysaccharide
  • soluble epoxide hydrolase inhibitor

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice. / Zhou, Yong; Liu, Tian; Duan, Jia Xi; Li, Ping; Sun, Guo Ying; Liu, Yong Ping; Zhang, Jun; Dong, Liang; Lee, Kin Sing Stephen; Hammock, Bruce D.; Jiang, Jian Xin; Guan, Cha Xiang.

In: Shock, Vol. 47, No. 5, 01.05.2017, p. 638-645.

Research output: Contribution to journalArticle

Zhou, Y, Liu, T, Duan, JX, Li, P, Sun, GY, Liu, YP, Zhang, J, Dong, L, Lee, KSS, Hammock, BD, Jiang, JX & Guan, CX 2017, 'Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice', Shock, vol. 47, no. 5, pp. 638-645. https://doi.org/10.1097/SHK.0000000000000767
Zhou, Yong ; Liu, Tian ; Duan, Jia Xi ; Li, Ping ; Sun, Guo Ying ; Liu, Yong Ping ; Zhang, Jun ; Dong, Liang ; Lee, Kin Sing Stephen ; Hammock, Bruce D. ; Jiang, Jian Xin ; Guan, Cha Xiang. / Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice. In: Shock. 2017 ; Vol. 47, No. 5. pp. 638-645.
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AU - Duan, Jia Xi

AU - Li, Ping

AU - Sun, Guo Ying

AU - Liu, Yong Ping

AU - Zhang, Jun

AU - Dong, Liang

AU - Lee, Kin Sing Stephen

AU - Hammock, Bruce D.

AU - Jiang, Jian Xin

AU - Guan, Cha Xiang

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