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IL-13 regulates IL-17C expression by suppressing NF-κB-mediated transcriptional activation in airway epithelial cells.

Abstract：

:The cytokine interleukin (IL)-17C is highly expressed in epithelial tissues and involved in innate immune responses; however, the regulation of IL-17C expression in the airways remains poorly understood. Here, we show that IL-1β strongly induces both IL-17C mRNA and protein expression in primary normal human bronchial epithelial cells. Conversely, IL-13 significantly reduced the IL-1β-induced IL-17C expression. Attenuation of the nuclear factor (NF)-κB-signaling pathway using an NF-κB-subunit p65-specific small-interfering RNA (siRNA), reduced IL-1β-induced IL-17C expression, demonstrating the importance of NF-κB signaling in IL-17C regulation. The inhibitory effects of IL-13 on IL-17C expression were abolished when the Janus kinase (JAK)/signal transducer and activator of transcription 6 (STAT6)-signaling pathway was impaired, using either the JAK inhibitor ruxolitinib or a STAT6-specific siRNA. Western blot analysis demonstrated that IL-1β promoted both IκB-α phosphorylation and degradation, and p65 nuclear translocation. Although IL-13 induced STAT6 phosphorylation and nuclear translocation, it did not affect the activation of the IL-1β-mediated NF-κB-pathway. Using chromatin immunoprecipitation, we confirmed that IL-1β enhanced p65 binding to regions within the IL-17C promoter that flank putative NF-κB-binding sites (-130/-120 and -157/-147). Interestingly, IL-13 treatment reduced the IL-1β-mediated p65 binding to these regions. These findings demonstrate that NF-κB-mediated transcriptional mechanisms are critically involved in the IL-1β-mediated IL-17C induction, and that IL-13 negatively regulates this induction by suppressing NF-κB-based transcriptional activation.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Yamanaka K,Fujisawa T,Kusagaya H,Mori K,Niwa M,Furuhashi K,Kono M,Hamada E,Suda T,Maekawa M

doi

10.1016/j.bbrc.2017.11.207

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

1534-1540

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)32384-7

journal_volume

495

pub_type

杂志文章

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IL-13 regulates IL-17C expression by suppressing NF-κB-mediated transcriptional activation in airway epithelial cells.