IL-1β: a key modulator in asthmatic airway smooth muscle hyper-reactivity

Abstract

Asthma is a chronic inflammatory disorder of the airway. It is characterized by airway hyper-reactivity, which can be attributed to the chronically inflamed airway. However, the molecular mechanism is still under investigation. In this article, we have shown that IL-1β is a key molecule that can orchestrate both Toll-like receptor and muscarinic receptor pathways, and that antagonizing the function of IL-1β has a promising future as a potential drug target for asthma treatment. IL-1β can activate NF-κB pathways via Toll-like receptors, and NF-κB will eventually transactivate the genes of cytokines, chemokines, proteins of the complement system, adhesion molecules and immune receptors involved in inflammation. IL-1β can activate eosinophils, which can release major basic protein (MBP) to antagonize the M₂ receptors leading to excessive acetylcholine release. Acetylcholine has an effect on M₃ receptors, which are related to airway smooth muscle contraction and mucus production. IL-1β is reported to activate COX-2 resulting in heterologous desensitization of adenylate cyclase and impairs relaxation of the ASM. IL-1β is involved in mediation of neutrophilic inflammation. Identification of the prominent role of IL-1β in asthma could lead to successful use of anti-IL1β agents.

Keywords:

• asthma
• IL-1β
• hyperreactivity
• muscarinic receptors
• toll-like receptor

Financial & competing interests disclosure

This work was funded by the Science & Technology Program of Sichuan Province (Grant number: 2009SZ0226, 2014FZ0103,2015JQO027,2015ZR0160), the health department of Sichuan province (Grant number: 100491, 120111), Chengdu City Science and technology project (Grant number: 11PPYB010SF-289) and Young Scholars foundation of Sichuan Provincial People’s Hospital (Grant number: 30305030606, 30305030859). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Asthma, usually triggered by a variety of allergens or irritants, is a common airway disease characterized by recurring and reversible inflammation and obstruction of bronchi.

• The contraction of airway smooth muscle (ASM) leads to a narrowing passage of the airway, exacerbated by increased mucus production.

• Toll-like receptors play a key part in both innate and adaptive immune systems.

• The cholinergic effect on lungs includes the induction of contraction of the ASM, mucus secretion and blood vessel dilation.

• IL-1β can activate NF-κB pathways via Toll-like receptors, and NF-κB will eventually transactivate the genes of cytokines, chemokines, proteins of the complement system, adhesion molecules and immune receptors involved in inflammation.

• IL-1β can activate eosinophils, which can release MBP to antagonize the M₂ receptors leading to excessive acetylcholine release. Acetylcholine has an effect on M₃ receptors, which are related to ASM contraction and mucus production.

• IL-1β is reported to activate COX-2, resulting in heterologous desensitization of AC and impaired relaxation of the ASM.

• IL-1β is involved in mediation of neutrophilic inflammation. Identification of the prominent role of IL-1β in asthma could lead to successful use of anti-IL-1β agents.