title: [Losartan modulates T helper type 1 cells and T helper type 17 cells-mediated responses in a mouse model of lipopolysaccharide-induced acute lung injury].
abstract: OBJECTIVE
  To assess the effect of losartan, angiotensin II receptor type 1 (AT1) receptor antagonist, on the pulmonary T helper (Th) cell polarization response in acute lung injury (ALI) mice.
  
  
  METHODS
  C57BL/6 mice were randomized into control group, ALI group and ALI + losartan group, which respectively were administrated with phosphate buffered saline(PBS), 2 mg/kg lipopolysaccharide (LPS) and 2 mg/kg LPS as well as 15 mg/kg losartan 30 minutes before intratracheal injection of LPS. Lung wet weight/body weight (LW/BW) was recorded to assess the severity of lung injury. The mRNA expression levels of T-box expressed in T cells (T-bet), GATA-binding protein-3 (GATA-3) and retinoid-related orphan nuclear receptor γt (RORγt) were quantitatively measured by real-time polymerase chain reaction (RT-PCR). Meanwhile, interleukin 6(IL-6), interferon γ (IFNγ) , IL-4 and IL-17 in lung homogenates were assessed by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  (1) LW/BW was significantly increased in ALI group compared with ALI+losartan group. (2) Histologically, widespread interstitial thickening with edema, severe alveolar hemorrhage, and diffuse interstitial infiltration of inflammatory cells were observed in the ALI group. Whereas, losartan effectively attenuated the LPS-induced alveolar hemorrhage and leukocyte infiltration. (3) The levels of IL-6 in lung tissue were significantly enhanced in the LPS-induced ALI mice, while it markedly decreased in ALI +losartan group. (4) The mRNA expression of T-bet and RORγt was up-regulated in ALI mice at 24 h and 48 h compared to control group (P < 0.05). There was no significant difference in the expression of GATA-3. In addition, compared with ALI group, ALI mice with pretreatment of losartan resulted in significantly reduced mRNA expression of T-bet at 24 h and 48 h and RORγt mRNA expression at 48 h (all P < 0.05). (5) Meanwhile, the levels of IFNγ, IL-4, IL-17 and IL-6 in lung tissue were significantly enhanced at 24 h and 48 h in the LPS-induced ALI mice. In addition, both IFNγ and IL-17 in lung tissue at 24 h and 48 h decreased significantly in losartan-pretreated mice compared with the ALI mice. However, the level of IL-4 in lungs was similar in ALI group and ALI+losartan group.
  
  
  CONCLUSIONS
  Losartan has a protective effect on LPS-induced ALI, which may be partly dependent on suppressions of Th1 and Th17 polarization response.
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Pengshu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China. Email: haiboq2000@gmail.com.
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
mesh_terms: D055371:Acute Lung Injury; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma; D020381:Interleukin-17; D015847:Interleukin-4; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019808:Losartan / Q000009:adverse effects*; D008168:Lung; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020381:Interleukin-17; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007371:Interferon-gamma; D019808:Losartan