Losartan inhibits conventional dendritic cell maturation and Th1 and             Th17 polarization responses: Νovel mechanisms of preventive effects on lipopolysaccharide-induced             acute lung injury.
Acute lung injury (ALI) remains one of major causes of morbidity and mortality in intensive care medicine. The lack of efficient pharmacological interventions contributes to the high mortality rate of ALI. Losartan, an antagonist of angiotensin II (Ang II) type 1 receptor, is a potent therapeutic drug for ALI. Recent reports suggest that losartan inhibits the maturation of dendritic cells (DCs), impairs T-helper (Th) 1 immune response and ultimately attenuates inﬂammation in several Ang II-mediated inflammatory diseases. However, the possible protective mechanisms of losartan in ALI remain poorly understood. This study was aimed to deﬁne the effect of losartan on the frequency and phenotype of respiratory conventional DCs (cDCs) and Th cells polarization in lipopolysaccharide (LPS)-induced ALI mice. Results demonstrate that early after induction of LPS-induced ALI, cDCs expressing modest amounts of CD80 rapidly accumulated in the lungs. In addition, polarized Th1 and Th17 responses were markedly increased in LPS-induced ALI mice at 24 and 48 h. Of note, losartan led to inhibition of respiratory cDCs maturation at 6 h and suppressed Th1 and Th17 polarization responses compared with ALI mice at 24 and 48 h. Collectively, our findings may provide a novel and, at least, partial explanation for the protective effects by which losartan inhibits lung cDCs maturation and suppresses Th1 and Th17 immune responses.
Department of Critical Care Medicine, Nanjing Zhong-Da Hospital, Southeast University School of Medicine, Nanjing 210009, PR China.
Jun
J
Liu
Peng-Shu
PS
Zhang
Qing
Q
Yu
Ling
L
Liu
Yi
Y
Yang
Feng-Mei
FM
Guo
Hai-Bo
HB
Qiu
D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008954:Models, Biological; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D008070:Lipopolysaccharides; D019808:Losartan