26 February 2018 : Laboratory Research
Curcumin Attenuates Pulmonary Inflammation in Lipopolysaccharide Induced Acute Lung Injury in Neonatal Rat Model by Activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) PathwayKeping Cheng1ABCDEF, Aijuan Yang1ABDF, Xiaohui Hu1ACF, Dongbo Zhu1ACE, Kaizhong Liu2ABCDEFG*
Med Sci Monit 2018; 24: LBR1178-1184
BACKGROUND: This study aimed to investigate the therapeutic effect of curcumin in lipopolysaccharide (LPS) induced neonatal acute lung injury (ALI) and the possibly associated molecular mechanisms.
MATERIAL AND METHODS: ALI neonatal animal model was established by using LPS. Curcumin and/or peroxisome proliferator-activated receptor γ (PPARγ) inhibitor BADGE (bisphenol A diglycidyl ether) were administrated to animals. Lung edema was evaluated by PaO2 and lung wet/dry weight ratio (W/D) measurements. EMSA was used to determine the PPARγ activity. Levels of high-mobility group box 1 (HMGB1), secretory receptor for advanced glycation end products (RAGE), tumor necrosis factor α (TNFα), interleukin 6 (IL6), and transforming growth factor b1 (TGFβ1) in bronchoalveolar lavage fluid (BALF) were examined by ELISA. Western blotting was used to evaluate the expression levels of HMGB1, RAGE, heme oxygenase 1 (HO1), TNFα, IL6, and TGFβ1 in lung tissue.
RESULTS: Curcumin administration significantly improved lung function by increasing PaO2 and decreasing W/D in neonatal ALI rats. Curcumin treatment upregulated the PPARγ activity and expression level of HO1 which were suppressed in lung tissue of neonatal ALI rats. Elevated levels of HMGB1, RAGE, TNFα, IL6, and TGFβ1 in both lung tissue and BALF from neonatal ALI rats were decreased dramatically by curcumin treatment. PPARγ inhibitor BADGE administration impaired curcumin’s alleviation on lung edema, inhibitory effects on inflammatory cytokine expression and recovery of PPARg/HO1 signaling activation.
CONCLUSIONS: Curcumin alleviated lung edema in LPS-induced ALI by inhibiting inflammation which was induced by PPARγ/HO1 regulated-HMGB1/RAGE pro-inflammatory pathway.
Keywords: acute lung injury, Curcumin, PPAR gamma
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