title: IKKβ/NFκBp65 activated by interleukin-13 targets the autophagy-related genes LC3B and beclin 1 in fibroblasts co-cultured with breast cancer cells.
abstract: Interleukin-13 (IL-13), a Th2 cytokine, plays an important role in fibrosis, inflammation, tissue hyperresponsiveness and tumor development. Although studies have demonstrated that IL-13 exerts its roles through signal transducer and activator of transcription 6 (STAT6) signaling pathway, recent studies have revealed that I kappa B kinase (IKK)/nuclear factor kappa B (NFκB) pathway may also be involved in. The aim of this study was to investigate whether IL-13 delivers signals to IKKβ/NFκBp65 and whether autophagy genes are IL-13-induced the activation of NFκBp65 transcriptional targets in fibroblasts of breast tumor stroma. We examined the phosphorylation of IKKβ, the activation of NFκBp65 and NFκBp65-targeted autophagy genes in fibroblasts co-cultured with breast cancer cells under the condition of IL-13 stimulation. Results of this study showed that IL-13 induced IKKβ phosphorylation in the fibroblast line ESF co-cultured with breast cancer cell line BT474, and subsequently NFκBp65 was activated and aimed at beclin 1 and microtubule-associated protein 1 light chain 3 B (MAP1LC3B or LC3B) in these ESF cells. BMS345541, an inhibitor of IKK/NFκB pathway, significantly inhibited the IL-13-induced the activation of NFκB and also inhibited NFκB-targeted beclin 1 and LC3B expression. Our results suggest that IL-13 regulates beclin 1 and LC3B expression through IKKβ/NFκBp65 in fibroblasts co-cultured with breast cancer cells, and IL-13 plays role in activating IKKβ/NFκBp65.
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Shi
authors.affiliation: Molecular Laboratory, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Guan-Yun
authors.initials: GY
authors.lastname: Qi
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Meng
keywords: beclin 1; breast cancer; fibroblast; inhibitor of κB kinase β; interleukin-13; microtubule-associated protein 1 light chain 3 β; nuclear factor κB