Ethanol changes sensitivity of Kupffer cells to endotoxin.
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Accession number;03A0846830
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| Title;Ethanol changes sensitivity of Kupffer cells to endotoxin. |
| Author;
YAMASHINA SHUNHEI
(Juntendo Univ., School of Medicine, JPN)
IKEJIMA KEN'ICHI
(Juntendo Univ., School of Medicine, JPN)
ENOMOTO NOBUYUKI
(Juntendo Univ., School of Medicine, JPN)
TAKEI YOSHIYUKI
(Juntendo Univ., School of Medicine, JPN)
SATO NOBUHIRO
(Juntendo Univ., School of Medicine, JPN)
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Journal Title;Japanese Journal of Alcohol Studies & Drug Dependence
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Journal Code:G0193B
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ISSN:1341-8963
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VOL.38;NO.5;PAGE.415-424(2003)
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| Figure&Table&Reference;FIG.4, REF.25 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Gut-derived endotoxin plays an important role in alcoholic liver injury. Intestinal sterilization with antibiotics (polymyxin B and neomycin) or inactivation of Kupffer cells with gadolinium chloride can prevent early alcohol-induced liver injury in the Tsukamoto-French model. Although short-term administration of alcohol enhances endotoxin hepatotoxicity, a majority of studies report that short-term ethanol inactivates Kupffer cells. It is therefore paradoxical that Kupffer cells are involved in alcoholic liver injury based on in vivo data with gadolinium chloride and antibiotics, yet ethanol blunts activation of isolated Kupffer cells. Accordingly, this review focuses on understanding this paradox by studying the temporal effect of ethanol in vivo on the response of subsequently isolated Kupffer cells. Mice were given ethanol intragastrically, and LPS was injected later. One hour after ethanol treatment, serum transaminases after LPS were 60% of control, while ethanol increased these parameters about 3-fold 21 hours after ethanol. Pretreatment with antibiotics blocked these effects of ethanol. Two hours after ethanol administration, the LPS-induced increases in intracellular calcium concentration and TNF.ALPHA. release by Kupffer cells was diminished by 50% of control, and these parameters were reciprocally enhanced two-fold at 24 hours. Sterilization of the gut with antibiotics blocked both effects of ethanol on intracellular calcium concentration and TNF.ALPHA. release. Twenty-four hours after ethanol, CD14 in Kupffer cells was elevated to about five-fold. In Kupffer cells from mice treated with ethanol 1 hour earlier, IRAK expression and activity and NF.KAPPA.B were decreased to 50-60% of control. In contrast, in Kupffer cells from mice treated with ethanol 21 hours earlier, LPS-induced TNF.ALPHA. production, expression and activity of IRAK were increased 1.5-fold over controls, while NF.KAPPA.B activation was elevated 3-fold.... (author abst.) |
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