| | |  | | | | Record from Web of Science® | | | | | | |
| Alcohol causes both tolerance and sensitization of rat Kupffer cells via mechanisms dependent on endotoxin |
|
|
| Author(s): Enomoto N, Ikejima K, Bradford B, Rivera C, Kono H, Brenner DA, Thurman RG |
| Source: GASTROENTEROLOGY Volume: 115 Issue: 2 Pages: 443-451 Published: AUG 1998 |
| Times Cited: 124 References: 34 |
| Abstract: Background & Aims: Ethanol causes both tolerance and sensitization of Kupffer cells. This study was designed to evaluate temporal effects of ethanol in an attempt to understand this paradox. Methods: Rats were given ethanol (4 g/kg body wt) intragastrically, and Kupffer cells were isolated 0-48 hours later. After addition of lipopolysaccharide (LPS), intracellular calcium concentration ([Ca2+](i)) was measured using a microspectrofluorometer with the fluorescent indicator fura-2, and tumor necrosis factor alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western and Northern analysis. Results: Two hours after ethanol administration, the LPS-induced increase in [Ca2+](i) and TNF-alpha release by Kupffer cells was diminished by 50%, and these parameters were reciprocally enhanced twofold at 24 hours. Sterilization of the gut with antibiotics blocked all effects of ethanol on [Ca2+](i) and TNF-alpha release completely. Twenty-four hours after ethanol, CD14 in Kupffer cells was elevated about fivefold. Conclusions: Kupffer cells isolated from rats early after ethanol exhibited tolerance to LPS, whereas sensitization was observed later. It is likely that both of these phenomena are caused by gut-derived endotoxin and that sensitization in Kupffer cells is caused by increases in CD14. |
| Document Type: Article |
| Language: English |
| Reprint Address: Thurman, RG (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA |
Addresses:
1. Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA
2. Univ N Carolina, Dept Med, Div Digest Dis & Nutr, Chapel Hill, NC 27599 USA |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA |
| Subject Category: Gastroenterology & Hepatology |
| IDS Number: 108YE |
| ISSN: 0016-5085 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |