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:	Yang, R., Lin, Q., Gao, H.B., Zhang, P.
Format:	Online
Language:	English
Published:	Associação Brasileira de Divulgação Científica 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051180/

id	pubmed-4051180
recordtype	oai_dc
spelling	pubmed-40511802014-06-10 Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells Yang, R. Lin, Q. Gao, H.B. Zhang, P. Biomedical Sciences 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. Associação Brasileira de Divulgação Científica 2014-02-17 /pmc/articles/PMC4051180/ /pubmed/24519125 http://dx.doi.org/10.1590/1414-431X20133346 Text en http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yang, R. Lin, Q. Gao, H.B. Zhang, P.
spellingShingle	Yang, R. Lin, Q. Gao, H.B. Zhang, P. Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells
author_facet	Yang, R. Lin, Q. Gao, H.B. Zhang, P.
author_sort	Yang, R.
title	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_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_sort	stress-related hormone norepinephrine induces interleukin-6 expression in ges-1 cells
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.
publisher	Associação Brasileira de Divulgação Científica
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051180/
_version_	1612098893844054016

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

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