MicroRNA‑16 inhibits interleukin‑13‑induced inflammatory cytokine secretion and mucus production in nasal epithelial cells by suppressing the IκB kinase β/nuclear factor‑κB pathway

Gao,Yueqiu; Yu,Zhengzheng

doi:10.3892/mmr.2018.9394

MicroRNA‑16 inhibits interleukin‑13‑induced inflammatory cytokine secretion and mucus production in nasal epithelial cells by suppressing the IκB kinase β/nuclear factor‑κB pathway

Authors:
- Yueqiu Gao
- Zhengzheng Yu
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Affiliations: Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China
Published online on: August 17, 2018 https://doi.org/10.3892/mmr.2018.9394
Pages: 4042-4050

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Abstract

Chronic inflammation of the nasal mucosal tissue plays important roles in the pathogenesis of allergic rhinitis (AR). Aberrantly expressed microRNAs (miRNAs) have been found to have strong associations with inflammatory reactions in allergic diseases; however, its functional significance and molecular mechanism underlying in AR remains unclear. The aim of the present study was to investigate the biological functions of miRNA and reveal its underlying molecular mechanisms in AR. miRNA microarray was performed to analyze miRNAs expression levels in 3 paired nasal mucosal samples from patients with AR and a control group. Subsequently, human nasal epithelial cells (JME/CF15) were used as an in vitro model to further explore the functions of miRNAs. Microarray data revealed that miR‑16 was one of the miRNAs being most significantly downregulated. Interleukin (IL)‑13 stimulation gradually decreased the levels of miR‑16 in JME/CF15 cells. Moreover, upregulation of miR‑16 inhibited inflammatory cytokines, including granulocyte‑macrophage colony‑stimulating factor (GM‑CSF), eotaxin, IL‑1β, IL‑6 and IL‑10 in IL‑13‑treated JME/CF15 cells. Furthermore, overexpression of miR‑16 significantly decreased the mRNA and protein expression levels of mucin 5AC (MUC5AC). IκB kinase β (IKKβ) was identified as a direct target of miR‑16 and its expression was negatively regulated by miR‑16 at mRNA and protein levels. Notably, forced expression of miR‑16 blocked NF‑κB signaling by decreasing the expression of nuclear p‑p65 and p‑IκB‑α, as well as increasing the expression of IκB‑α in IL‑13‑treated nasal epithelial cells. Moreover, enhanced IKKβ reactivated the NF‑κB pathway that was blocked by miR‑16 mimics and then effectively suppressed the miR‑16‑mediated inhibitory effects on inflammatory response. These findings suggested that miR‑16 suppressed the inflammatory response by inhibiting the activation of IKKβ/NF‑κB signaling pathways.

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