Publications (2)2.59 Total impact
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ABSTRACT: The antagonism or genetic deletion of adenosine A(2A) receptors has been shown to exacerbate tissue damage in acute lung injury. Caffeine, a widely consumed behavioral drug, acts as a non-selective antagonist of A(2A) receptor and also has additional pharmacological effects. Thus, the protective vs. deleterious effects of caffeine in acute lung injury should be evaluated. In a murine oleic acid-induced model of acute lung injury, we found that chronic caffeine treatment by drinking water (0.1g/l or 0.25g/l for 2 weeks before acute lung injury) or acute caffeine treatment at high dose (i.p. 50mg/kg, injection, 30min before acute lung injury) significantly attenuated the lung edema, hemorrhage, neutrophil recruitment as well as the inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) expressions in both of the wild type (WT) and A(2A) receptor knockout (KO) mice. This profile was accompanied by increased cAMP levels and up-regulation of A2B receptor mRNAs in the lungs. In contrast, acute caffeine treatment at low dose (i.p. 5mg/kg or 15mg/kg, injection, 30min before acute lung injury) enhanced the inflammation and lung damage in WT mice with decreasing cAMP but not in A(2A) receptor KO mice. These results indicate that caffeine either enhances lung damage by antagonizing A(2A) receptor or exerts protection against lung damage via A(2A) receptor-independent mechanisms, depending on the timing of exposure (chronic vs. acute) and dose of administration (low vs. high). These findings provide new insight of caffeine in acute lung injury and highlight the potential benefit and strategy of caffeine intake or administration for preventing acute lung injury.European journal of pharmacology 03/2011; 654(3):295-303. · 2.59 Impact Factor
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ABSTRACT: TGFβ/smad pathway is recognized as an important signal pathway to promote the pathogenesis of atherosclerosis (AS). Peroxisome proliferator-activated receptor γ (PPARγ) activation is considered to be important in modulating AS. Herein, we investigated the regulation of PPARγ on c-Ski, the repressor of TGFβ/smad pathway, in rat AS model and cultured vascular smooth muscle cells (VSMCs). c-Ski mRNA and protein expression were detected by real-time PCR and Western blot, respectively, in vivo and in vitro with treatment of PPARγ agonist rosiglitazone and antagonist GW9662. The proliferation and collagen secretion of VSMCs after c-Ski transfection were investigated. The underlying mechanism was further investigated by online program NUBIScan and luciferase reporter gene analysis. Results showed that both mRNA and protein expressions of c-Ski in the AS lesions was down-regulated in vivo, while in cultured VSMCs, c-Ski transfection significantly suppressed the proliferation and collagen secretion of rat VSMCs. Rosiglitazone significantly up-regulated mRNA and protein levels of c-Ski in VSMCs, which could be blocked by GW9662. Online NUBIScan analysis suggested possible PPARγ binding sites in the promoter region of c-Ski. In addition, luciferase activity of c-Ski reporter gene was also increased obviously in the presence of rosiglitazone. These results indicate that c-Ski is one of the newly found target genes of PPARγ and thus involved in the anti-AS effect of PPARγ.Sheng li xue bao: [Acta physiologica Sinica] 02/2011; 63(1):62-8.