Z Gastroenterol 2020; 58(01): e64
DOI: 10.1055/s-0039-3402278
Poster Visit Session V Viral Hepatitis and Immunology: Saturday, February 15, 2020, 11:00 am – 11:45 am, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

The inflammatory mediators IL-1β and TNFα prevent CDCA-induced BSEP expression via induction of chemokines

C Lohr
1   Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
,
L Missing
1   Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
,
C Ehlting
1   Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
,
D Häussinger
1   Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
,
JG Bode
1   Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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    Question:

    Cholestasis is a common complication in patients with sepsis and systemic inflammatory response syndrome. In this context IL1β and TNFα mediated downregulation of the expression of the bile salt export pump (BSEP) is known to be important (Luster et al., 1994, Roelofsen et al., 1995). However, the importance of the relevance of chemokines in this regard is unclear, and the elucidation of their significance for the inhibition of bile-salt-induced upregulation of the expression of BSEP is the subject of the present studies.

    Methods:

    primary hepatocytes isolated from murine liver and the human hepatoma cell line HepaRG were stimulated with different concentrations of TNFα and IL-1β, CDCA and SB 225002 either alone or in combination. Afterwards the gene expression of BSEP, CXCL1 – 3 and 5 was determined by real-time PCR.

    Results:

    the results of the present study indicate that TNFα and IL-1β stimulate the expression of the CXCR2 ligands CXCL 1 – 3 and 5, which is even further enhanced in the presence of CDCA. Moreover in primary murine hepatocytes as well as in HepaRG, inhibition of the chemokine receptor CXCR2 by the compound SB225002 supposed to be specifically inhibit CXCR2 was able to block the inhibitory effects of IL-1β and partially of TNFa on CDCA-induced upregulation of BSEP expression.

    Conclusion:

    the data summarized herein suggest that TNFa and IL-1b both at least in part mediate their inhibitory effects on bile salt-induced upregulation of BSEP expression via induction of the expression of the CXCR2 ligands CXCL1 – 3 and 5.

    References:

    [1] LUSTER, M. I., GERMOLEC, D. R., YOSHIDA, T., KAYAMA, F. & THOMPSON, M. 1994. Endotoxin-induced cytokine gene expression and excretion in the liver. Hepatology,19,480 – 8.

    [2] ROELOFSEN, H., SCHOEMAKER, B., BAKKER, C., OTTENHOFF, R., JANSEN, P. L. & ELFERINK, R. P. 1995. Impaired hepatocanalicular organic anion transport in endotoxemic rats. Am J Physiol,269,G427 – 34.


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