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Blocking angiotensin type 1 receptor modulates Thl-mediated and Th17-mediated responses in lipopolysaccharide-induced acute lung injury mice
Critical Care volume 18, Article number: P339 (2014)
Losartan, an antagonist of angiotensin II (Ang II) type 1 receptor, is a potential therapeutic drug for acute lung injury (ALI). Recent reports suggest that losartan inhibits T-helper (Th)-1 immune response and ultimately attenuates inflammation in several angiotensin II-mediated inflammatory diseases ,. However, the possible protective mechanisms of losartan in ALI remain poorly understood. This study was to assess the effect of losartan on the lung Th polarization response in ALI.
C57BL/6 mice were randomly divided into three groups: control group, ALI group and ALI + losartan group. ALI animals received 2 mg/kg LPS; ALI + losartan animals received 2 mg/kg LPS and 15 mg/kg losartan 30 minute before intratracheal injection of LPS. The pathological changes were examined under an optical microscope. The mRNA expression levels of T-bet, GATA-3 and RORγt were determined by quantitative real-time reverse transcriptase-polymerase chain reaction.
The increase in LW/BW induced by LPS was partly prevented by pretreated with losartan. Histologically, losartan effectively attenuated the LPS-induced lung hemorrhage, and leukocyte cell infiltration in the interstitium and alveolus. Meanwhile, the levels of IL-6 in lung tissue were significantly enhanced in the LPS-induced ALI mice. With pretreatment of ALI mice with losartan, the level of IL-6 in lungs markedly decreased. The mRNA expression of T-bet and RORγt was upregulated in ALI mice at 24 hours and 48 hours relative to normal mice (P < 0.05 vs. Con). There was no significant difference in the expression of GATA-3 among groups at 24 hours and 48 hours. Of note, pretreatment of ALI mice with losartan resulted in significantly reduced mRNA expression of T-bet at 24 hours and 48 hours and RORγt mRNA expression at 48 hours (P < 0.05 vs. ALI). Meanwhile, the levels of IFNγ, IL-4, IL-17 and IL-6 in lung tissue were significantly enhanced at 24 hours and 48 hours in the LPS-induced ALI mice. In addition, both IFNγ and IL-17 in lung tissue at 24 hours and 48 hours decreased significantly in losartan-pretreated mice compared with the ALI mice. With pretreatment of ALI mice with losartan, the level of IL-4 in lungs was not changed.
Ang II-induced Th1 and Th17 polarization response could upregulate inflammatory response and induce lung injury, and losartan may be a promising substance for clinical use in LPS-induced ALI.
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Supported by the Research Project CPSFG 2013M542578, JSPSFG 1301005A, SYS201251 and 2013NJZS50.
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Liu, J., Li, W. Blocking angiotensin type 1 receptor modulates Thl-mediated and Th17-mediated responses in lipopolysaccharide-induced acute lung injury mice. Crit Care 18 (Suppl 1), P339 (2014). https://doi.org/10.1186/cc13529
- Acute Lung Injury
- Polarization Response
- Losartan Group
- Acute Lung Injury Group