Dexamethasone enhances mallory body formation in drug-primed mouse liver.
In a clinical study in which patients with alcoholic hepatitis were treated with prednisone for 1 month, posttreatment liver biopsies showed diminished inflammation, but Mallory bodies were not diminished. This suggested that steroid treatment may reduce inflammation by inhibiting NFkappaB activation. Sparing of Mallory bodies suggests that NFkappaB activation may not be involved mechanistically in Mallory body formation. To test this idea, we induced Mallory body formation in drug-primed mice with or without dexamethasone treatment. As predicted, dexamethasone decreased NFkappaB activation; however, Mallory body formation was increased. Surprisingly, TNFalpha and iNOS, which normally increase as a result of NFkappaB activation, were upregulated by the dexamethasone treatment. It was concluded that NFkappaB activation is not involved in Mallory body formation. Despite this, induced increases in TNFalpha, iNOS, c-jun/API and c-myc expression indicate that oxidative stress is likely involved in Mallory body formation.
Yuan
Q X
QX
Department of Pathology, Harbor-UCLA Medical Center, Torrance, California 90509, USA.
Nagao
Y
Y
French
B A
BA
Wan
Y J
YJ
French
S W
SW
D000818:Animals; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology*; D004095:Dihydropyridines / Q000633:toxicity; D004591:Electrophoresis, Polyacrylamide Gel; D005938:Glucocorticoids / Q000494:pharmacology*; D002479:Inclusion Bodies / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007633:Keratins / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008854:Microscopy, Electron; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects / Q000378:metabolism
D004095:Dihydropyridines; D005938:Glucocorticoids; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; C061879:diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate; D007633:Keratins; D003907:Dexamethasone