Db. Hill et al., Increased monocyte nuclear factor-kappa B activation and tumor necrosis factor production in alcoholic hepatitis, J LA CL MED, 135(5), 2000, pp. 387-395
Citations number
68
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Increased tumor necrosis factor-a activity has been reported in patients wi
th alcoholic hepatitis and is implicated in its pathogenesis. The aim of th
is study was to investigate potential mechanisms of increased tumor necrosi
s factor-a activity in alcoholic hepatitis. Monocyte nuclear factor-kb acti
vity was assessed by electrophoretic mobility shift assay, monocyte tumor n
ecrosis factor-a mRNA was semiquantitatively assessed by reverse transcript
ase polymerase chain reaction, and tumor necrosis factor-a in monocyte cult
ure supernatants was measured. There was significantly greater spontaneous
nuclear factor-kB activity in the monocytes of 6 patients with alcoholic he
patitis as compared with that in the monocytes of control subjects. There w
as spontaneous tumor necrosis factor-a mRNA and tumor necrosis factor-a rel
ease from the monocytes of patients with alcoholic hepatitis but not from t
he monocytes of normal subjects. Endotoxin increased nuclear factor-kB acti
vity and induced tumor necrosis factor-a mRNA and tumor necrosis factor-a r
elease from normal subjects' monocytes, Endotoxin further increased nuclear
factor-ks activity, tumor necrosis factor-a mRNA, and tumor necrosis facto
r-a release from the monocytes of patients with alcoholic hepatitis. Supers
hift assays indicate that the monocyte nuclear factor-kB activation involve
s the p50 and p65 subunits, Dysregulated tumor necrosis factor-a metabolism
in alcoholic hepatitis monocytes is associated with increased nuclear fact
or-kB activity and tumor necrosis factor-a mRNA expression.