Medizinische Universität Graz - Research portal
Selected Publication:
Enomoto, N; Yamashina, S; Goto, M; Schemmer, P; Thurman, RG.
Desensitization to LPS after ethanol involves the effect of endotoxin on voltage-dependent calcium channels.
Am J Physiol. 1999; 277(6 Pt 1):G1251-G1258
Doi: 10.1152/ajpgi.1999.277.6.G1251
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Schemmer Peter
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- Abstract:
- Hepatic macrophages are sensitized to alcohol in 24 h due to increases in the endotoxin receptor, CD14; however, desensitization to lipopolysaccharide (LPS), which occurred earlier, could not be explained by changes in CD14. Therefore, the purpose of this work was to attempt to understand factors responsible for ethanol-induced desensitization to LPS in hepatic macrophages. Rats were given ethanol (5 g/kg body wt) intragastrically, and hepatic macrophages were isolated 2 h later. After addition of endotoxin, intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using fura 2 and tumor necrosis factor (TNF)-alpha was measured by ELISA. Ethanol given 2 h before injection of LPS totally prevented liver injury and blunted LPS-induced increases in [Ca(2+)](i) and TNF-alpha in hepatic macrophages. Furthermore, the protein kinase C (PKC) agonist phorbol 12-myristate 13-acetate and acute ethanol treatment both activated PKC and largely prevented the influx of [Ca(2+)](i) caused by LPS. Sterilization of the gut with antibiotics completely blocked all effects of ethanol on [Ca(2+)](i) and TNF-alpha release. Thus ethanol-induced desensitization of hepatic macrophages correlates with gut-derived endotoxin after ethanol and involves the effect of PKC on voltage-dependent Ca(2+) channels.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calcium - metabolism
- Calcium Channels - physiology
- Central Nervous System Depressants - blood
- Central Nervous System Depressants - pharmacology
- Enzyme Inhibitors - pharmacology
- Ethanol - blood
- Ethanol - pharmacology
- Female -
- Lipopolysaccharides - blood
- Lipopolysaccharides - pharmacology
- Liver - chemistry
- Liver - cytology
- Liver - enzymology
- Macrophages - chemistry
- Macrophages - drug effects
- Macrophages - enzymology
- Microcystins -
- Peptides, Cyclic - pharmacology
- Protein Kinase C - metabolism
- Rats -
- Rats, Sprague-Dawley -
- Survival Analysis -
- Transaminases - blood
- Tumor Necrosis Factor-alpha - metabolism
- Find related publications in this database (Keywords)
- intracellular calcium
- tumor necrosis factor-alpha
- protein kinase C
- lipopolysaccharide