Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation of human colon cancer cells.

Oncotarget
Han LiuJames H Doroshow

Abstract

Human colon cancers express higher levels of NADPH oxidase 1 [NOX1] than adjacent normal epithelium. It has been suggested that reactive oxygen species [ROS] derived from NOX1 contribute to DNA damage and neoplastic transformation in the colon, particularly during chronic inflammatory stress. However, the mechanism(s) underlying increased NOX1 expression in malignant tumors or chronic inflammatory states involving the intestine are poorly characterized. We examined the effects of two pro-inflammatory cytokines, IL-4 and IL-13, on the regulation of NOX1. NOX1 expression was increased 4- to 5-fold in a time- and concentration-dependent manner by both cytokines in human colon cancer cell lines when a functional Type II IL-4 receptor was present. Increased NOX1 transcription following IL-4/IL-13 exposure was mediated by JAK1/STAT6 signaling, was associated with a ROS-related inhibition of protein tyrosine phosphatase activity, and was dependent upon activation and specific binding of GATA3 to the NOX1 promoter. NOX1-mediated ROS production increased cell cycle progression through S-phase leading to a significant increase in cellular proliferation. Evaluation of twenty pairs of surgically-resected colon cancers and their associated ...Continue Reading

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Citations

Apr 24, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Viviani MendesAngelica Thomaz Vieira
Jun 23, 2020·Oncology Letters·Yael Delgado-RamirezSonia Leon-Cabrera
Feb 6, 2020·Antioxidants & Redox Signaling·Mariam M KonatéJames H Doroshow
Jun 21, 2018·Frontiers in Immunology·Caroline AndrewsScott K Durum
Mar 30, 2019·Neural Plasticity·Ying BiLei Zhao
Jan 17, 2021·International Journal of Molecular Sciences·Xujun SongMarko Kornmann
Sep 25, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yongzhong WuJames H Doroshow
Dec 30, 2020·International Journal of Molecular Sciences·Reyes Gamez-BelmonteChristoph Becker
Jul 9, 2021·Frontiers in Cell and Developmental Biology·Chris M Li, Zhibin Chen

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Datasets Mentioned

BETA
GSE20916

Methods Mentioned

BETA
transfection
nuclear translocation
immunoprecipitation
PCR
Assay
protein assay
FACS
flow cytometry

Software Mentioned

FlowJo
Oncomine

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