Intraabdominal sepsis down-regulates transcription of sodium taurocholate cotransporter and multidrug resistance-associated protein in rats

Autor: Jodi Chen, Clifford S. Deutschman, Patrick K. Kim, Kenneth M. Andrejko
Rok vydání: 2000
Předmět:
Male
Organic anion transporter 1
Transcription
Genetic
medicine.medical_treatment
Critical Care and Intensive Care Medicine
Rats
Sprague-Dawley
chemistry.chemical_compound
Mice
Cecum
Hyperbilirubinemia
biology
Bile acid
Symporters
Multidrug resistance-associated protein 2
Interleukin
Multidrug Resistance-Associated Protein 2
Systemic Inflammatory Response Syndrome
Cytokine
Liver
Emergency Medicine
Multidrug Resistance-Associated Proteins
Taurocholic Acid
medicine.medical_specialty
ATP Binding Cassette Transporter
Subfamily B
medicine.drug_class
Organic Anion Transporters
Sodium-Dependent
Cholestasis
Intrahepatic
digestive system
Sepsis
Cholestasis
Internal medicine
medicine
Animals
RNA
Messenger
Ligation
Ion Transport
business.industry
Interleukin-6
Sodium
Membrane Transport Proteins
Taurocholic acid
medicine.disease
Rats
Endocrinology
chemistry
Gene Expression Regulation
Intestinal Perforation
biology.protein
business
Carrier Proteins
Zdroj: Shock (Augusta, Ga.). 14(2)
ISSN: 1073-2322
Popis: Hepatic dysfunction in sepsis is characterized by hyperbilirubinemia and intrahepatic cholestasis. We hypothesize that sepsis causes decreased hepatic transcription of the bile acid transporter sodium taurocholate cotransporter (Ntcp) and the organic anion transporter multidrug resistance-associated protein (Mrp2) and that interleukin (IL)-6 is important in the down-regulation of Ntcp and Mrp2 expression. Male Sprague-Dawley rats underwent induction of mild, nonlethal sepsis by cecal ligation and single puncture (CLP) or fulminant sepsis by cecal ligation and double puncture (2CLP). Hepatic transcription of Ntcp and Mrp2 rapidly decreased after CLP or 2CLP. Seventy-two hours later, transcription was 60% of baseline in CLP and 14% of baseline in 2CLP. Serum bilirubin was elevated from 24 h onward and cholestasis was observed on fixed liver specimens at 24, 48, and 72 h after 2CLP but not after CLP. Steady-state Ntcp and Mrp2 mRNA was decreased in IL-6-treated cultured hepatocytes and in normal rats given 1 mg/kg intravenous IL-6. We conclude that 1) Ntcp and Mrp2 transcription is down-regulated transiently after CLP and persistently after 2CLP; 2) 2CLP results in hyperbilirubinemia and cholestasis, in part due to persistently decreased transcription of Ntcp and Mrp2; and 3) altered Ntcp and Mrp2 transcription is mediated in part by IL-6.
Databáze: OpenAIRE
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