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

• Published in: Brazilian journal of medical and biological research 2014-02, Vol.47 (2), p.101-109
• Main Authors: Yang, R, Lin, Q, Gao, H B, Zhang, P
• Format: Article
• Language: English
• Subjects: BIOLOGY; Biomedical Sciences; Cancer; Cell Line; Development and progression; Enzyme-Linked Immunosorbent Assay; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gene Expression Regulation - physiology; GES-1 cells; Humans; Interleukin-6; Interleukin-6 - genetics; Interleukin-6 - metabolism; MEDICINE, RESEARCH & EXPERIMENTAL; NF-kappa B - metabolism; Norepinephrine; Norepinephrine - metabolism; Norepinephrine - pharmacology; Psychological aspects; Real-Time Polymerase Chain Reaction; Receptors, Adrenergic, beta - metabolism; RNA, Messenger - metabolism; Signal Transduction - physiology; Transcription Factors - physiology; Up-Regulation
• ISSN: 0100-879X; 1414-431X; 1414-431X; 0100-879X
• DOI: 10.1590/1414-431X20133346

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.