Gene expression of tumor necrosis factor α and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients

Authors

  • Javier Crespo,

    Corresponding author
    1. Institute of Digestive Diseases and University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
    • Servicio Aparato Digestivo, Hospital Universitario “Marqués de Valdecilla,” Av. Valdecilla s/n, Santander. E-39008. Cantabria. Spain. fax: (34) 073442202544
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  • Amalía Cayón,

    1. Institute of Digestive Diseases and University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
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  • Pedro Fernández-Gil,

    1. Institute of Digestive Diseases and University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
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  • Manuel Hernández-Guerra,

    1. Institute of Digestive Diseases and University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
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  • Marta Mayorga,

    1. Department of Pathology, University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
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  • Agustín Domínguez-Díez,

    1. Institute of Digestive Diseases and University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
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  • José Carlos Fernández-Escalante,

    1. Institute of Digestive Diseases and University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
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  • Fernando Pons-Romero

    1. Institute of Digestive Diseases and University Hospital “Marqués de Valdecilla,” School of Medicine, Santander, Spain.
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Abstract

The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor α (TNF-α) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-α and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-α, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF-α was found in patients with NASH in hepatic tissue (0.65 ± 0.54) and in peripheral fat (0.43 ± 0.45); in the control samples, the mRNA expression was 0.28 ± 0.32, P < .007, and 0.26 ± 0.22, P < .018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 ± 1.81 vs. 1.56 ± 1.17; P < .05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF-α in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-α mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF-α system may be involved in the pathogenesis of NASH.

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