2011
DOI: 10.1016/j.bcp.2011.04.017
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Regulation of drug transporter expression by oncostatin M in human hepatocytes

Abstract: The cytokine oncostatin M (OSM) is a member of the interleukin (IL)-6 family, known to down-regulate expression of drug metabolizing cytochromes P-450 in human hepatocytes. The present study was designed to determine whether OSM may also impair expression of sinusoidal and canalicular drug transporters, which constitute important determinants of drug hepatic clearance. Exposure of primary human hepatocytes to OSM down-regulated mRNA levels of major sinusoidal solute carrier (SLC) influx transporters, including… Show more

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Cited by 35 publications
(12 citation statements)
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References 42 publications
(24 reference statements)
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“…Several reasons might explain the poor prediction of interindividual variability of hepatic OATP2B1 expression, although systematic ascertainment of covariates in our liver bank was guaranteed [51] (Table S1 in Additional file 1). Other non-genetic factors like cytokines [52] may affect OATP2B1 expression. Moreover, unidentified transcription factors, genetic variation in those genes as well as epigenetics such as DNA methylation [53] or regulation by microRNA [54] may contribute to the interindividual variability of OATP2B1.…”
Section: Discussionmentioning
confidence: 99%
“…Several reasons might explain the poor prediction of interindividual variability of hepatic OATP2B1 expression, although systematic ascertainment of covariates in our liver bank was guaranteed [51] (Table S1 in Additional file 1). Other non-genetic factors like cytokines [52] may affect OATP2B1 expression. Moreover, unidentified transcription factors, genetic variation in those genes as well as epigenetics such as DNA methylation [53] or regulation by microRNA [54] may contribute to the interindividual variability of OATP2B1.…”
Section: Discussionmentioning
confidence: 99%
“…mRNAs encoding the pro‐inflammatory cytokines IL‐6, IL‐1β and TNF‐α were increased to 2.5‐ to 3‐fold of control in preterm placentas with infection (Petrovic et al, ). Treatment of primary human hepatocytes with the cytokines TNF‐α, IL‐6 and oncostatin M down‐regulated OATP1B1, OATP1B3, OATP2B1 and OAT2 expression, while IL‐1β and IFN‐γ repressed OATP1B1, OATP1B3 and OATP2B1 (Le Vee et al, , ,b). A strength of these studies was the use of primary cells and it appears that there may be selectivity in the regulatory actions of particular cytokines on individual transporters.…”
Section: Regulation Of Oat/oatp Transporters In Disease Statesmentioning
confidence: 99%
“…In vitro studies in human hepatocytes also suggest a role for proinflammatory cytokines in the regulation of a wide range of drug transporters other than P-gp, such as OATPs, MRPs, OATs, and OCTs (Le Vee et al, 2008, 2011; Vee et al, 2009). However, in vivo data is lacking, and more studies are needed to explore the role of immune response in the regulation of drug transporters and its effect on the pharmacokinetics of drugs.…”
Section: Immunological Response and Drug Transportmentioning
confidence: 99%