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

• Published in: Hepatology (Baltimore, Md.) Vol. 34; no. 6; pp. 1158 - 1163
• Main Authors: Crespo, Javier, Cay[oacute]n, Amal[iacute]a, Fern[aacute]ndez-Gil, Pedro, Hern[aacute]ndez-Guerra, Manuel, Mayorga, Marta, Dom[iacute]nguez-D[iacute]ez, Agust[iacute]n, Fern[aacute]ndez-Escalante, Jos[eacute] Carlos, Pons-Romero, Fernando
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.12.2001
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1053/jhep.2001.29628

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 [plusmn] 0.54) and in peripheral fat (0.43 [plusmn] 0.45); in the control samples, the mRNA expression was 0.28 [plusmn] 0.32, P [lt ] .007, and 0.26 [plusmn] 0.22, P [lt ] .018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 [plusmn] 1.81 vs. 1.56 [plusmn] 1.17; P [lt ] .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. (HEPATOLOGY 2001;34:1158-1163.)