IKKβ/NFκBp65 activated by interleukin-13 targets the autophagy-related genes LC3B and beclin 1 in fibroblasts co-cultured with breast cancer cells

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 (NF kappa B) pathway may also be involved in. The aim of this study was to investigate whether IL-13 delivers signals to IKK beta/NF kappa Bp65 and whether autophagy genes are IL-13-induced the activation of NF kappa Bp65 transcriptional targets in fibroblasts of breast tumor stroma. We examined the phosphorylation of IKK beta, the activation of NF kappa Bp65 and NF kappa Bp65-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 IKK beta phosphorylation in the fibroblast line ESF co-cultured with breast cancer cell line BT474, and subsequently NF kappa Bp65 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/NF kappa B pathway, significantly inhibited the IL-13-induced the activation of NF kappa B and also inhibited NF kappa B-targeted beclin 1 and LC3B expression. Our results suggest that IL-13 regulates beclin 1 and LC3B expression through IKK beta/NF kappa Bp65 in fibroblasts co-cultured with breast cancer cells, and IL-13 plays role in activating IKK beta/NF kappa Bp65.