Glucocorticoid-Dependent Induction of Interleukin-6 Receptor Expression in Human Hepatocytes Facilitates Interleukin-6 Stimulation of Amino Acid Transport

Fischer, Craig P.; Bode, Barrie P.; Takahashi, Kazuhisa; Tanabe, Kenneth K.; Souba, Wiley W.

doi:10.1097/00000658-199605000-00017

Cited by 24 publications

(8 citation statements)

References 25 publications

(1 reference statement)

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“…No changes in b-actin mRNA levels were observed ( Figure 3b, lower panel). Our ®nding that Dex enhances the expression of IL-6R mRNA levels is in concert with previous studies (Mori et al, 1998;Fischer et al, 1996).…”

Section: Effect Of Dex On Interleukin-6 Receptor (Il-6r) Genesupporting

confidence: 93%

Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays

et al. 2002

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Our previous studies have characterized Dexamethasone (Dex)-induced apoptotic signaling pathways in multiple myeloma (MM) cells; however, related transcriptional events are not fully de®ned. In the present study, gene expression pro®les of Dex-treated MM cells were determined using oligonucleotide arrays. Dex triggers early transient induction of many genes involved in cell defense/repair-machinery. This is followed by induction of genes known to mediate cell death and repression of growth/survival-related genes. The molecular and genetic alterations associated with Dex resistance in MM cells are also unknown. We compared the gene expression pro®les of Dex-sensitive and Dex-resistant MM cells and identi®ed a number of genes which may confer Dexresistance. Finally, gene pro®ling of freshly isolated MM patient cells validates our in vitro MM cell line data, con®rming an in vivo relevance of these studies. Collectively, these ®ndings provide insights into the basic mechanisms of Dex activity against MM, as well as mechanisms of Dex-resistance in MM cells. These studies may therefore allow improved therapeutic uses of Dex, based upon targeting genes that regulate MM cell growth and survival.

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Section: Effect Of Dex On Interleukin-6 Receptor (Il-6r) Genesupporting

confidence: 93%

Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays

et al. 2002

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“…Indeed, treatment of cells with IL-6 is sufficient to alter the expression of amino acid transporters and amino acid transport in vitro. 32,63 It has been proposed that changes in fetal gene expression resulting from MIA may be driven by IL-6-mediated activation of the transcription factor STAT3 in the fetal brain. 64 Furthermore, we have previously shown that the transcription factor NFκB, when activated indirectly by IL-6-mediated STAT3 activation (unpublished data) or directly by LPS, regulates inflammation-mediated dysregulation of hepatic SLC transporter expression.…”

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 99%

Poly(I:C) alters placental and fetal brain amino acid transport in a rat model of maternal immune activation

McColl

Piquette‐Miller

2019

American J Rep Immunol

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Problem Maternal immune activation (MIA) during pregnancy is associated with increased chances of neurodevelopmental disorders including schizophrenia and autism spectrum disorder (ASD). However, the exact mechanism through which MIA contributes to altered neurodevelopment is unknown. Due to the important role that amino acids play in neurodevelopment, altered amino acid transport could play a role in neurodevelopmental disorders. Indeed, altered plasma concentrations of multiple amino acids have been reported in individuals with ASD or schizophrenia. Therefore, our objective was to determine whether virally mediated MIA induces changes in amino acid transporters in the placenta and fetal brain. Method of study Pregnant rats were administered poly(I:C) on gestational day 14, and placental and fetal tissues were collected 6, 24, and 48 hours later. Amino acid transporter expression was measured in the placenta and fetal brain using qPCR, Western blotting, and Simple Western. Free amino acid concentrations in the fetal brain were quantified using HPLC. Results Poly(I:C) increased mRNA expression of several amino acid transporters in the placenta and fetal brain over these timepoints. Conversely, poly(I:C) imposed significant decreases in the protein expression of ASCT1 and EAAT2 in placenta and expression of SNAT5, EAAT1, and GLYT1 in fetal brain. Functional consequences of altered transporter expression were demonstrated through widespread changes in the concentrations of free amino acids in the fetal brains. Conclusion Together, these results represent novel findings with the poly(I:C) MIA model and contribute to the understanding of how MIA during pregnancy potentially leads to neurodevelopmental disorders.

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“…Hepatocytes cultured from the 'inflamed' (postlaparotomy) animals showed a similar response suggesting that the augmenting effect of Dex on serum APR proteins occurred in the liver where there was evidence of GC-mediated regulation of the glycosylation step during protein synthesis. For example, incubation of human hepatic cells with 50-100-nM concentrations of Dex markedly increases cytokine-induced transcriptional activation of the serum amyloid A gene (73) as well as hepatic amino acid transport (74). Additionally, a single intraperitoneal injection of Dex to normal rats increases hepatic IL-6 receptor mRNA in harvested hepatocytes fivefold within 12 h (75).…”

Section: Glucocorticoid Enhancement Of Inflammationmentioning

confidence: 99%

Glucocorticoid regulation of the inflammatory response to injury

Yeager

Guyre

Munck

2004

Acta Anaesthesiol Scand

110

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During the first half of the 20th century, physiologists were interested in the adrenal glands primarily because adrenalectomized animals failed to survive even mild degrees of systemic stress. It eventually became clear that hormones secreted by the adrenal cortex were critical for survival and, in this context, adrenal cortical hormones were widely considered to support or stimulate important responses to stress or injury. With the purification and manufacture of adrenal cortical hormones in the 1930s and 1940s, clinicians suddenly discovered the potent anti-inflammatory actions of glucocorticoids (GCs). This dramatic, and unexpected, discovery has dominated clinical and laboratory research into GC actions throughout the second half of the 20th century. More recent research is again reporting GC-induced stimulatory effects on a variety of inflammatory response components. These effects are usually observed at low GC concentrations, close to concentrations that are observed in vivo during basal, unstimulated states. For example, GC-mediated stimulation has been reported for the hepatic acute-phase response, for cytokine secretion, expression of cytokine/chemokine receptors, and for the pro-inflammatory mediator, macrophage migration inhibition factor. It seems clear that the long-held clinical view that GCs act solely as anti-inflammatory agents needs to be re-assessed. Varying doses of GCs do not lead simply to varying degrees of inflammation suppression, but rather GCs can exert a full range of effects from permissive to stimulatory to suppressive.

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Glucocorticoid-Dependent Induction of Interleukin-6 Receptor Expression in Human Hepatocytes Facilitates Interleukin-6 Stimulation of Amino Acid Transport

Cited by 24 publications

References 25 publications

Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays

Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays

Poly(I:C) alters placental and fetal brain amino acid transport in a rat model of maternal immune activation

Glucocorticoid regulation of the inflammatory response to injury

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