Protection against liver injury by PGE1 or anti-TNF-alpha is associated with a reduction of TNF-R1 expression in hepatocytes.
BACKGROUND
Tumour necrosis factor-alpha (TNF-5) has been shown to exacerbate or protect against liver injury in different experimental models. In a previous study, we observed that enhancement of TNF-alpha expression in hepatocytes by prostaglandin E1 (PGE1) pre-administration induced iNOS expression and cytoprotection against experimental liver injury in rats. Nevertheless, the reduction of TNF-alpha bioactivity by anti-TNF-alpha antibodies also reduced liver injury by D-GalN. The purpose of the present study was to evaluate whether protection by PGE1 or anti-TNF-alpha was related to a common effect on the membrane-bound TNF-alpha receptor expression.


METHODS
Liver injury was induced in male Wistar rats by intraperitoneal injection of D-galactosamine (D-GalN) (1 g/kg). PGE1 or anti-TNF-alpha was administered at 30 or 60 min before D-GalN, respectively. Liver injury was evaluated by alanine aminotransferase (ALT) activity in serum and histological examination in liver sections. TNF-alpha was determined by ELISA in serum. The expression of TNF-alpha receptor type 1 (TNF-R1) and TNF-alpha receptor type 2 (TNF-R2) in hepatocytes was assessed by immunohistochemistry and immunoprecipitation + Western-blot analysis.


RESULTS
PGE1 or anti-TNF-alpha reduced liver injury induced by D-GalN. Although PGE1 enhanced and anti-TNF-alpha reduced TNF-alpha concentration in serum, both protective treatments reduced the expression of TNF-R1 in hepatocytes. TNF-R2 was not detected in our experimental conditions.


CONCLUSIONS
Our study showed that reduction of liver injury by PGE1 or anti-TNF-alpha antibodies was related to a reduction of TNF-R1 expression in hepatocytes.
Lozano
J M
JM
Unidad Clínica Aparato Digestivo, Servicio Anatomía Patológica, Hospital Universitario Reina Sofía, Av Menéndez Pidal s/n, Córdoba, Spain.
Collado
J A
JA
Medina
T
T
Muntané
J
J
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D005688:Galactosamine / Q000009:adverse effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D000410:Alanine Transaminase; D000527:Alprostadil