English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y 2  complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates  MUC5AC  gene expression via the inhibition of G α q-induced Ca 2+  signaling. IL-1ra inhibited IL-1 α  protein expression and secretion, and vice versa. Interestingly, ATP/P2Y 2 -induced IL-1ra and IL-1 α  secretion were both mediated by PLC β 3. A dominant-negative mutation in the PDZ-binding domain of PLC β 3 inhibited ATP/P2Y 2 -induced IL-1ra and IL-1 α  secretion. IL-1 α  in the presence of the ATP/P2Y 2  complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y 2  complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y 2 -induced  MUC5AC  gene expression, through inhibition of IL-1 α  secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.

IL-1ra Secreted by ATP-Induced P2Y2Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation