کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5666542 1591534 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
IL-1β upregulates Muc5ac expression via NF-κB-induced HIF-1α in asthma
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
IL-1β upregulates Muc5ac expression via NF-κB-induced HIF-1α in asthma
چکیده انگلیسی


- IL-1β is related to Muc5ac in asthma.
- IL-1β increased Muc5ac expression.
- HIF-1α is essential to IL-1β-induced Muc5ac expression in asthma.
- HIF-1α could bind to Muc5ac promoter.
- NF-κB is responsible for IL-1β-upregulated HIF-1α in asthma.

The manifest and important feature in respiratory diseases, including asthma and COPD (chronic obstructive pulmonary disease), is the increased numbers and hypersecretion of goblet cells and overexpression of mucins, especially Muc5ac. Many proinflammatory cytokines play important roles in goblet cell metaplasia and overproduction of Muc5ac. However, the effect of IL-1β on Muc5ac expression in asthma remains unknown. Here, we detected the correlation between IL-1β and Muc5ac in asthma patients and further explored the mechanism of IL-1β-induced Muc5ac overexpression. Our results showed that Muc5ac and IL-1β were up-regulated in 41 patients with asthma and that Muc5ac overexpression was related with IL-1β in asthma (R2 = 0.668, p ≪ 0.001). Furthermore, the correlation between IL-1β and Muc5ac is higher in severe group than that in moderate group. In vitro experiments with normal human bronchial epithelial cells (NHBECs) showed that IL-1β up-regulated Muc5ac expression in NHBEC in a time- and dosage-dependent manner. Hypoxia-induced HIF-1α was responsible for Muc5ac expression mediated by IL-1β. Knocking down HIF-1α by siRNA decreased Muc5ac expression under hypoxia even in IL-1β-treated NHBEC cells. Luciferase reporter assay showed that HIF-1α enhanced Muc5ac promoter activity in HEK293T cells. HIF-1α could specifically bind to the promoter of Muc5ac by EMSA. The correlation among IL-1β, HIF-1α and Muc5ac was observed in patients with asthma. Mechanically, NF-κB activation was essential to IL-1β-induced HIF-1α upregulation via the canonical pathway of NF-κB. The level of nuclear p65, a subunit of NF-κB, was obviously increased in NHBEC cells under IL-1β treatment. IL-1β did not change either HIF-1α or Muc5ac expression when inhibiting NF-κB signaling with Bay11-7082, an inhibitor of NF-κB. Collectively, we concluded that IL-1β up-regulated Muc5ac expression via NF-κB-induced HIF-1α in asthma and provided a potential therapeutic target for asthma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunology Letters - Volume 192, December 2017, Pages 20-26
نویسندگان
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