title: Cyclooxygenase-2 promotes hepatocellular apoptosis by interacting with TNF-α and IL-6 in the pathogenesis of nonalcoholic steatohepatitis in rats.
abstract: OBJECTIVE
  The underlying mechanisms of nonalcoholic steatohepatitis (NASH) are poorly understood, and little is known about hepatocellular apoptosis in NASH. Cyclooxygenase (COX)-2, the key enzyme in eicosanoid metabolism, is highly expressed in NASH. COX-2 can also regulate the release of mediators of inflammation, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. The aim of our study was to evaluate the effects of COX-2 on hepatocellular apoptosis and the mechanism of the action in the pathogenesis of NASH in rats.
  
  
  METHODS
  Sprague-Dawley rats were fed a high-fat diet (HFD) or standard diet for 8 and 12 weeks. COX-2 and cytokines expression in hepatic tissue and TNF-α and IL-6 levels in serum were measured at 8 and 12 weeks. Moreover, celecoxib (10 mg/kg body weight once a day) was administered to rats for 4 weeks to inhibit the expression of COX-2. Liver pathology was assessed by hematoxylin and eosin (H&E) stain and electron microscopy. Hepatocyte apoptosis was evaluated by TUNEL staining.
  
  
  RESULTS
  COX-2 messenger RNA and protein were highly expressed in livers of HFD rats and were correlated with the severity of steatohepatitis (R = 0.82, p < 0.01). COX-2 upregulation was preceded by increases in TNF-α and IL-6. The level of hepatocellular apoptosis was significantly higher in HFD rats than in the control rats. The hepatocellular apoptosis was suppressed by the inhibition of COX-2.
  
  
  CONCLUSIONS
  COX-2 may promote hepatocellular apoptosis by interacting with TNF-α and IL-6 in NASH in rats.
authors: Department of Infectious Diseases, Huashan Hospital of Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China.
authors: Qi
authors: Q
authors: Cheng
authors: Ning
authors: N
authors: Li
authors: Mingquan
authors: M
authors: Chen
authors: Jianming
authors: J
authors: Zheng
authors: Zhiping
authors: Z
authors: Qian
authors: Xinyu
authors: X
authors: Wang
authors: Chong
authors: C
authors: Huang
authors: Shuchang
authors: S
authors: Xu
authors: Guangfeng
authors: G
authors: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D022781:Hepatocytes / Q000473:pathology*; D015850:Interleukin-6 / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D000068579:Celecoxib
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