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- W3028628916 abstract "Objective To explore the effects of let-7 inhibitor(anti-let-7) on airway inflammation in rats with asthma,and to investigate the mechanisms of let-7 in the development of asthma.Methods A total of 32 mice were randomly assigned to control group (group A,n=8),asthma group (group B,n=8),treatment control group(group C,n=8) and treatment group (group D,n=8),respectively.Groups B,C and D were sensitized with ovalbumin(OVA) for establishment of mouse asthma model.Group A was treated with normal saline orally.Group D was administered with anti-let-7 prior to challenge,for suppression of endogenous let-7e expression,while scrambled-siRNA was injecled in group C for treatment control.The cell count,let-7e in pulmonary tissues and interleukin-10 (11-10) in bronchoalveolar lavage fluid (BALF) were detected.A549 cells,the lung cancer cells,were transfected with anti-let-7 in vitro followed by measurement of let-7e expression and IL-IO in cell culture supernatants.Luciferase report assay was employed to assess if let-7e targeted at IL-10.Results Compared with group A,groups B and C significantly increased in the total cell count [(20.32±5.33) x 109/L and (24.74±6.69) x 109/L vs (7.12± 1.88) x 109/L,both P<O.01] and eosinophil count [(6.45±2.5) x109/L and (7.12±2.66) x109/L vs (0.04±0.01) x109/L.both P<O.01] in BALF as well as let-7e of Iung tissues (by 3.83-fold and 3.27-fold,both P<O.01).When compared with group C,group D significantly reduced in total cell count [(13.85±3.74) x109/L vs (24.74±6.69) x109/L,P<0.05] and eosinophil count[(2.15±1.13) x109/L vs (7.12±2.66) x109/L,P<0.05] in BALF,and in let-7e of lung; tissues [(0.45±0.22) vs (3.28±0.45),P<0.05],while markedly increased the level of IL-IO in BALF [(4.68±0.85) vs (1.70±0.29),P<O.O1].Additionally,transfection of A549 cells using anti-let-7 resulted in reduction of let-7e expression [(0.22±0.03) vs (1.00±0.11),P<O.O1] and elevation of 11-10 in the supernatant [(2.58±0.35) vs (1.00± 0.15),P<O.01].Moreover.over-expression of let-7e led to significantly suppressed luciferase activity of IL-10 reporter vector [(0.59±0.06) vs (1.00±0.03),P<O.01],but did not affect the mutant IL-10 reporter vector.Conclusion The anti-let-7 can markedly inhibit airway inflammation in mice with asthma,possibly by targeting at let-7 and inhibition of IL-10.Key words: Asthma; MicroRNAs; Interleukin-10; Airway inflammation" @default.
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- W3028628916 date "2012-12-15" @default.
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- W3028628916 title "Role and mechanism of let-7 in airway inflammation in mice with asthma" @default.
- W3028628916 doi "https://doi.org/10.3760/cma.j.issn.1674-1927.2012.06.008" @default.
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