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.