Lipopolysaccharide treatment downregulates the expression of the pregnane X receptor, cyp3a11 and mdr1a genes in mouse placenta

Chen, Yuan-Hua; Wang, Jianping; Wang, Hua; Sun, Mei-Fang; Wei, Ling-Zhen; Wei, Wei; D, Xu

doi:10.1016/j.tox.2005.03.011

Cited by 49 publications

(24 citation statements)

References 44 publications

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“…Our findings differ from prior literature reports noting transporter down-regulation during inflammation caused by inflammatory cytokines such as TNF-␣, IL-6, and endotoxin (i.e., LPS) in rats (Sukhai et al, 2001;Chen et al, 2005;Wang et al, 2005) and human primary placental cells (Evseenko et al, 2007). We offer several possible explanations for these differences: the impact of LPS-induced inflammation on drug transporters has yet to be evaluated at different gestational stages, and previous reports have indicated that preterm placentas respond differently to LPS than those at term, specifically in their patterns of cytokine release (Holcberg et al, 2007).…”

Section: Mason Et Alcontrasting

confidence: 99%

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Mason

Buhimschi²,

Buhimschi³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Fetal drug exposure is determined by the type and concentration of placental transporters, and their regulation is central to the development of new treatments and delivery strategies for pregnant women and their fetuses. We tested the expression of several clinically important transporters in the human placenta associated with various pregnancy conditions (i.e., labor, preeclampsia, and preterm labor-inflammation). Placentas were obtained from five groups of women at the time of primary cesarean section: 1) term no labor; 2) term labor; 3) preterm no labor (delivered for severe preeclampsia); 4) preterm labor without inflammation (PTLNI); and 5) preterm labor with inflammation (PTLI). Samples were analyzed by Western blot and immunohistochemistry to identify changes in protein expression. Relative mRNA expression was determined by quantitative real-time polymerase chain reaction. A functional genomic approach was used to identify placental gene expression and elucidate molecular events that underlie the given condition. Placental expression of ATP-binding cassette transporters from women in labor and women with preeclampsia was unaltered. Multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) and mRNA expression increased in placentas of women with preterm labor with inflammation. Molecular pathways of genes up-regulated in PTLI samples included cytokinecytokine receptor interactions and inflammatory response compared with those in the PTLNI group. The mRNA expression of MDR1 and BCRP was correlated with that of interleukin-8, which also increased significantly in PTLI samples. These data suggest that the transfer of drugs across the placenta may be altered in preterm pregnancy conditions associated with inflammation through changes in MDR1 and BCRP.

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Section: Mason Et Alcontrasting

confidence: 99%

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Mason

Buhimschi²,

Buhimschi³

et al. 2011

Drug Metab Dispos

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“…It is assumed that cellular toxin activated receptors, including the PXR-SXR (pregnane X receptor) and the CAR (constitutive androstane receptor), play a major role in this response (see Refs. 195,351,403), which is an integrated phenomenon including the regulation of metabolic enzymes as well (25,55,195). A general and coordinated upregulation of the multidrug transporters and CYP enzymes may significantly alter several drug effects.…”

Section: Adaptive Chemoimmunity Response Memory and Hypersensitimentioning

confidence: 99%

“…Interestingly, under conditions resulting in major cell damage and increased endotoxin exposure (55,168), or in various forms of inflammatory bowel disease (IBD) (267), the expression of several MDR-ABC transporters is downregulated, which makes the affected tissues even more defenseless. The stress responsiveness of MDR1 expression is interestingly exemplified by the observation that this protein is measurably upregulated in nerve cells (normally hardly expressing MDR1) after limbic seizures (395).…”

Section: Adaptive Chemoimmunity Response Memory and Hypersensitimentioning

confidence: 99%

Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System

Sarkadi¹,

Homolya²,

Szakács³

et al. 2006

Physiological Reviews

646

532

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In this review we give an overview of the physiological functions of a group of ATP binding cassette (ABC) transporter proteins, which were discovered, and still referred to, as multidrug resistance (MDR) transporters. Although they indeed play an important role in cancer drug resistance, their major physiological function is to provide general protection against hydrophobic xenobiotics. With a highly conserved structure, membrane topology, and mechanism of action, these essential transporters are preserved throughout all living systems, from bacteria to human. We describe the general structural and mechanistic features of the human MDR-ABC transporters and introduce some of the basic methods that can be applied for the analysis of their expression, function, regulation, and modulation. We treat in detail the biochemistry, cell biology, and physiology of the ABCB1 (MDR1/P-glycoprotein) and the ABCG2 (MXR/BCRP) proteins and describe emerging information related to additional ABCB- and ABCG-type transporters with a potential role in drug and xenobiotic resistance. Throughout this review we demonstrate and emphasize the general network characteristics of the MDR-ABC transporters, functioning at the cellular and physiological tissue barriers. In addition, we suggest that multidrug transporters are essential parts of an innate defense system, the “chemoimmunity” network, which has a number of features reminiscent of classical immunology.

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“…Several transcription factors, including nuclear factor-B, c-Jun, and the pregnane-X-receptor (PXR in rodents; SXR in humans), have been shown to be involved in the regulation of MDR1/ mdr1a/mdr1b gene expression (Miao and Ding, 2003;Chen et al, 2005;Hayashi et al, 2005). For example, nuclear factor-B, a well-characterized transcription factor, has been shown to regulate mdr1a gene expression in rat brain microvessel endothelial cells treated with the HIV-1 transactivator protein Tat (Hayashi et al, 2005).…”

Section: Effect Of Gp120 On P-glycoprotein Expression In Astrocytes 1095mentioning

confidence: 99%

HIV-1 Viral Envelope Glycoprotein gp120 Triggers an Inflammatory Response in Cultured Rat Astrocytes and Regulates the Functional Expression of P-Glycoprotein

2006

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In this work, we examined the ability of gp120, a human immunodeficiency virus-1 (HIV-1) viral envelope glycoprotein, to trigger the innate immune response in astrocytes, an HIV-1 brain cellular target, and we investigated the functional expression of the ATP-binding cassette membrane transporter P-glycoprotein (P-gp) in primary cultures of rat astrocytes treated with gp120 or cytokines [tumor necrosis factor-␣ (TNF-␣), interleukin-1␤ (IL-1␤), and IL-6]. Standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium and D-mannitol uptake assays confirmed that HIV-1 96ZM651 gp120 treatment did not alter cell viability or membrane permeability. Semiquantitative reversetranscriptase polymerase chain reaction analysis and enzymelinked immunosorbent assay demonstrated increased TNF-␣, IL-1␤, and IL-6 mRNA and protein expression in cultures treated with HIV-1 96ZM651 gp120, suggesting in vitro activation of immune responses. Cytokine secretion was detected when CXCR4 but not CCR5 was inhibited with a specific antibody, implying that cytokine secretion is primarily mediated via CCR5 in astrocytes triggered with HIV-1 96ZM651 gp120. P-gp protein expression was increased in astrocyte cultures exposed to TNF-␣ (2.9-fold) or IL-1␤ (1.6-fold) but was decreased profoundly in the presence of IL-6 (8.9-fold), suggesting that IL-6 is primarily involved in modulating P-gp expression. In parallel, after HIV-1 96ZM651 gp120 treatment, immunoblotting analysis showed a significant decrease in P-gp expression (4.7-fold). Furthermore, the accumulation of two P-gp substrates, digoxin and saquinavir (an HIV-1 protease inhibitor), was enhanced (1.5-to 1.8-fold) in HIV-1 96ZM651 gp120-treated astrocyte monolayers but was not altered by P-gp inhibitors [e.g., valspodar (PSC833) and elacridar (GF120918)], suggesting a loss of transport activity. Taken together, these data imply that HIV-1 96ZM651 gp120 or cytokine treatment modulate P-gp functional expression in astrocytes, which may lead to complex drug-transporter interactions during HIV-1 encephalitis-associated immune responses.

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Lipopolysaccharide treatment downregulates the expression of the pregnane X receptor, cyp3a11 and mdr1a genes in mouse placenta

Cited by 49 publications

References 44 publications

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System

HIV-1 Viral Envelope Glycoprotein gp120 Triggers an Inflammatory Response in Cultured Rat Astrocytes and Regulates the Functional Expression of P-Glycoprotein

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