Dexamethasone inhibits the proliferation of hepatocytes and oval cells but not bile duct cells in rat liver.
Recent advances have implicated the importance of tumor necrosis factor (TNF) and interleukin 6 (IL-6) in the regulation of liver growth. Therefore, we studied how dexamethasone, a well-known inhibitor of these cytokines, influences the proliferation of different hepatic cell populations. As we expected, dexamethasone pretreatment suppressed the expression of both TNF and IL-6 after partial hepatectomy and significantly reduced the proliferative response of the hepatocytes. Furthermore, the proliferative response of hepatocytes could be rescued by IL-6 administration. Dexamethasone also severely diminished the induction and expansion of oval cells induced by the 2-acetylaminofluorene/partial hepatectomy (AAF/PH) protocol but did not have any effect on the proliferation of the bile duct cells stimulated by bile duct ligation. The differential inhibition of these two morphologically very similar cell types may be used to characterize divergent regulatory mechanisms responsible for the proliferative response of oval cells and adult bile epithelial cells.
1st. Institute of Pathology, Semmelweis Medical University, Budapest, Hungary.
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P
Nagy
A
A
Kiss
J
J
Schnur
S S
SS
Thorgeirsson
D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006498:Hepatectomy / Q000379:methods; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005938:Glucocorticoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone