Interferon tau-induced hepatocyte apoptosis in sheep

Hun Taek Kim, George Stoica, Fuller W. Bazer, Troy Ott

Research output: Contribution to journalArticle

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Abstract

Clinical applications of Type I interferon (IFN) are limited by adverse side effects mediated largely by unknown mechanisms. This study examined the mechanisms of acute hepatic injury in lambs treated with systemic administration of IFN-τ a Type I IFN. Liver tissues were collected at 24, 48, or 96 hours after treatment with either IFN-τ or saline. Histopathology revealed acute hepatopathy including cellular swelling, cytoplasmic aggregates, and apoptosis in all IFN-τ-treated lambs, which were accompanied by elevation of aspartate transaminase (AST) (P < .01). The number of apoptotic hepatocytes in IFN-τ-treated lambs was higher than for control lambs (P < .001). Immunohistochemistry for proliferating cell nuclear antigen (PCNA) revealed that IFN-τ induced hepatocyte growth arrest at the G0/G1 phase of the cell cycle and that the majority of hepatocytes in S or G2 phase were eliminated by apoptosis. We investigated expression of bax-α and bcl-2, acting as pro- and antiapoptotic molecules, in IFN-τ-induced apoptosis. Northern blot analysis revealed increased expression of bax-α messenger RNA (mRNA) in IFN-τ-treated lambs (P < .01) compared with control lambs, consistent with the expression pattern for bax-α protein. However, there was no detectable difference in expression of bcl-2 proteins between control and IFN-τ-treated lambs. The levels of bax-α associated with the mitochondria also increased during IFN-τ treatment. Bax-α immunostaining showed scattered immunoreactive hepatocytes with morphological hallmarks of apoptosis. These results suggest that IFN-τ induces growth arrest as well as apoptosis by regulating bax-α expression. These pathological effects of IFN- τ on sheep liver indicate potential mechanisms of Type I IFN-induced hepatotoxicity in animals and humans.

Original languageEnglish (US)
Pages (from-to)1275-1284
Number of pages10
JournalHepatology
Volume31
Issue number6
DOIs
StatePublished - Jan 1 2000

Fingerprint

Interferons
Hepatocytes
Sheep
Apoptosis
Interferon Type I
Liver
trophoblastin
bcl-2-Associated X Protein
Cell Cycle Resting Phase
G2 Phase
Proliferating Cell Nuclear Antigen
G1 Phase
Growth
Aspartate Aminotransferases
S Phase
Northern Blotting
Cell Cycle
Mitochondria
Immunohistochemistry
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Kim, Hun Taek ; Stoica, George ; Bazer, Fuller W. ; Ott, Troy. / Interferon tau-induced hepatocyte apoptosis in sheep. In: Hepatology. 2000 ; Vol. 31, No. 6. pp. 1275-1284.
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Kim, HT, Stoica, G, Bazer, FW & Ott, T 2000, 'Interferon tau-induced hepatocyte apoptosis in sheep', Hepatology, vol. 31, no. 6, pp. 1275-1284. https://doi.org/10.1053/jhep.2000.7476

Interferon tau-induced hepatocyte apoptosis in sheep. / Kim, Hun Taek; Stoica, George; Bazer, Fuller W.; Ott, Troy.

In: Hepatology, Vol. 31, No. 6, 01.01.2000, p. 1275-1284.

Research output: Contribution to journalArticle

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AU - Kim, Hun Taek

AU - Stoica, George

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AU - Ott, Troy

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