Decreased expression of P-glycoprotein in interleukin-1β and interleukin-6 treated rat hepatocytes

Abstract

Our data indicate that IL-6 and IL-1beta have suppressive effects on the expression and activity of PGP in cultured hepatocytes, likely occurring through distinct mechanisms. These cytokines may have a potential role in PGP regulation during inflammatory responses.

Downregulation of drug transport and metabolism in mice bearing extra-hepatic malignancies

“…In vitro studies in hepatoma cell lines illustrate the downregulation of Cyp3a11 exposed to the proinflammatory cytokines IL-6, IL-1b and TNF-a (Lee and Piquette-Miller, 2001;Sukhai et al, 2001). Furthermore, the inducible expression of CYP3A4 by rifampicin in human primary hepatocytes in culture is abrogated by the administration of IL-6, suggesting a central role of IL-6 in the repression of CYP3A (Muntane-Relat et al, 1995;Guillen et al, 1998).…”

“…As acute inflammation represses the expression of hepatic transporters, the expression levels of hepatic transporters in the presence of tumour-induced inflammation were determined (Hartmann et al, 2001(Hartmann et al, , 2002Lee and Piquette-Miller, 2001;Sukhai et al, 2001). The mRNA expression levels of relevant transporters were determined in mice bearing EHS sarcoma tumours and …”

“…Cytokines, in particular IL-6, reduce the mRNA and protein expressions of some hepatic transporters in vivo, and function in vitro (Hartmann et al, 2001;Lee and Piquette-Miller, 2001;Sukhai et al, 2001;Hartmann et al, 2002). Conversely, in tumours, studies have demonstrated an increase in the expression of some ABC superfamily transporters on tumour cells in response to IL-6, where they produce the multidrug-resistant tumour phenotype (Conze et al, 2001;Duan et al, 2002).…”

The Blood-Brain Barrier in Epilepsy

“…Most information on transporter regulation is available for P-gp, where signalling pathways have been shown to be present in various tissues (liver, kidney, intestine; (Ho & PiquetteMiller, 2006;Nawa et al, 2010;Thevenod et al, 2000). They also involve various signalling molecules: inflammatory mediators including TNF-, ET-1, IL1-, IL-6, NO; COX-2 (Dixit et al, 2005;Goralski et al, 2003;Nawa et al, 2010;Patel et al, 2002;Poller et al, 2010;Sukhai et al, 2001;Von Wedel-Parlow et al, 2009), nuclear receptors PXR, CAR, AhR, and GR (Bauer et al, 2004;Bauer et al, 2007;Geick et al, 2001;Narang et al, 2008;Wang et al, 2011;Wang et al, 2010), protein kinase C (Bauer et al, 2007;Chambers et al, 1990a;Chambers et al, 1990b;Hartz et al, 2004;Miller et al, 1998;Rigor et al, 2010), and NFkB (Bauer et al, 2007;Bentires-Alj et al, 2003;Kim et al, 2011;Liu et al, 2008;Thevenod et al, 2000;Yu et al, 2008). These pathways have been found in several diseases including Alzheimer's disease, HIV, and diabetes (Hartz et al, 2010;Hayashi et al, 2006;Nawa et al, 2010).…”

MCF-7 Breast Cancer Cell Line, a Model for the Study of the Association Between Inflammation and ABCG2-Mediated Multi Drug Resistance

“…Numerous in vitro and in vivo investigations reported that inflammation and proinflammatory cytokines are able to modulate the expression or function of different drug transporters including Multi-Drug Resistance transporter 1 (MDR1/ABCB1), Multidrug Resistance-associated Proteins (MRPs/ABCCs) and Lung-resistance Related Protein / Major Vault Protein (LRP/MVP). These modulations appeared to happen at various levels of expression including transcriptional, posttranscriptional, translational, and/or posttranslational levels (Bertilsson et al, 2001;Hartmann et al, 2002;Hirsch-Ernst et al, 1998; www.intechopen.com Piquette-Miller et al, 1998;Stein et al, 1997;Sukhai et al, 2001;Theron et al, 2003;Vos et al, 1998;Walther et al, 1994;Walther et al, 1995). The influence of proinflammatory cytokines (IL-1 , IL-6 and TNF-) on ABCG2 expression and function in human MCF-7 breast cancer cell line were studied using real-time PCR and flow cytometry, respectively.…”