Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients.
The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor alpha (TNF-alpha) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-alpha 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-alpha, 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-alpha 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-alpha in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-alpha 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-alpha system may be involved in the pathogenesis of NASH.
Crespo
J
J
Institute of Digestive Diseases, University Hospital Marqués de Valdecilla, School of Medicine, Santander, Spain. javiercrespo@teleline.es
Cayón
A
A
Fernández-Gil
P
P
Hernández-Guerra
M
M
Mayorga
M
M
Domínguez-Díez
A
A
Fernández-Escalante
J C
JC
Pons-Romero
F
F
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006505:Hepatitis / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015703:Antigens, CD; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha