Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells

In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise m...

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Main Authors: R. Yang, Q. Lin, H.B. Gao, P. Zhang
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2014-02-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2014000200101&lng=en&tlng=en
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author R. Yang
Q. Lin
H.B. Gao
P. Zhang
author_facet R. Yang
Q. Lin
H.B. Gao
P. Zhang
author_sort R. Yang
collection DOAJ
description In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.
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spelling doaj.art-c7fbfa9d831f409a842f3378938cbe9b2022-12-22T03:52:17ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2014-02-0147210110910.1590/1414-431X20133346S0100-879X2014000200101Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cellsR. YangQ. LinH.B. GaoP. ZhangIn the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2014000200101&lng=en&tlng=enNorepinephrineGES-1 cellsInterleukin-6
spellingShingle R. Yang
Q. Lin
H.B. Gao
P. Zhang
Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells
Brazilian Journal of Medical and Biological Research
Norepinephrine
GES-1 cells
Interleukin-6
title Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells
title_full Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells
title_fullStr Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells
title_full_unstemmed Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells
title_short Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells
title_sort stress related hormone norepinephrine induces interleukin 6 expression in ges 1 cells
topic Norepinephrine
GES-1 cells
Interleukin-6
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2014000200101&lng=en&tlng=en
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AT qlin stressrelatedhormonenorepinephrineinducesinterleukin6expressioninges1cells
AT hbgao stressrelatedhormonenorepinephrineinducesinterleukin6expressioninges1cells
AT pzhang stressrelatedhormonenorepinephrineinducesinterleukin6expressioninges1cells