Medizinische Universität Graz - Research portal
Selected Publication:
Enomoto, N; Yamashina, S; Schemmer, P; Rivera, CA; Bradford, BU; Enomoto, A; Brenner, DA; Thurman, RG.
Estriol sensitizes rat Kupffer cells via gut-derived endotoxin.
Am J Physiol. 1999; 277(3 Pt 1):G671-G677
Doi: 10.1152/ajpgi.1999.277.3.G671
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Schemmer Peter
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- Abstract:
- The relationship between gender and alcohol-induced liver disease is complex; however, endotoxin is most likely involved. Recently, it was reported that estriol activated Kupffer cells by upregulation of the endotoxin receptor CD14. Therefore, the purpose of this work was to study how estriol sensitizes Kupffer cells. Rats were given estriol (20 mg/kg ip), and Kupffer cells were isolated 24 h later. After addition of lipopolysaccharide (LPS), intracellular Ca2+ concentration was measured using a microspectrofluorometer with the fluorescent indicator fura 2, and tumor necrosis factor-alpha was measured by ELISA. CD14 was evaluated by Western analysis. One-half of the rats given estriol intraperitoneally 24 h before an injection of a sublethal dose of LPS (5 mg/kg) died within 24 h, whereas none of the control rats died. Mortality was prevented totally by sterilization of the gut with antibiotics. A similar pattern was obtained with liver histology and serum transaminases. Translocation of horseradish peroxidase was increased about threefold in gut segments by treatment with estriol. This increase was not altered by treatment with nonabsorbable antibiotics. On the other hand, endotoxin levels were increased to 60-70 pg/ml in plasma of rats treated with estriol. As expected, this increase was prevented (<20 pg/ml) by antibiotics. In isolated Kupffer cells, LPS-induced increases in intracellular Ca2+ concentration, tumor necrosis factor-alpha production, and CD14 were increased, as previously reported. All these phenomena were blocked by antibiotics. Therefore, it is concluded that estriol treatment in vivo sensitizes Kupffer cells to LPS via mechanisms dependent on increases in CD14. This is most likely due to elevated portal blood endotoxin caused by increased gut permeability.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Anti-Bacterial Agents - pharmacology
- Antigens, CD14 - metabolism
- Cell Death - physiology
- Cells, Cultured -
- Endotoxins - blood
- Endotoxins - physiology
- Estriol - pharmacology
- Female -
- Intestinal Mucosa - drug effects
- Intestinal Mucosa - metabolism
- Intestines - metabolism
- Kupffer Cells - drug effects
- Kupffer Cells - metabolism
- Kupffer Cells - physiology
- Lipopolysaccharides - pharmacology
- Liver - cytology
- Liver - drug effects
- Permeability -
- Portal Vein -
- Rats -
- Rats, Sprague-Dawley -
- Transaminases - blood
- Tumor Necrosis Factor-alpha - metabolism
- Find related publications in this database (Keywords)
- lipopolysaccharide
- tumor necrosis factor-alpha
- CD14
- intracellular calcium