The role of alpha7 nicotinic acetylcholine receptors in inflammatory bowel disease: involvement of different cellular pathways

ABSTRACT

Introduction: Autonomic imbalance plays a pivotal role in the pathophysiology of inflammatory bowel diseases (IBD). The central nervous system (CNS) cooperates dynamically with the immune system to regulate inflammation through humoral and neural pathways. In particular, acetylcholine (Ach), the main neurotransmitter in the vagus nerve, decreases the production of pro-inflammatory cytokines through a mechanism dependent on the α7 nicotinic Ach receptors (α7nAChRs).

Areas covered: Here, we review the evidence for involvement of the cholinergic anti-inflammatory pathway (CAP) in IBD. We also elaborate the role of α7nAChRs and subsequent cellular pathways in CAP. Finally, we review potential therapeutic implications of modulators of these receptors.

Expert opinion: Alpha7nAChR modulators possess both cognitive improving and anti-inflammatory properties. Although, these agents demonstrated therapeutic benefits in experimental models, their efficacy has not always been translated in clinical trials. Thus, development of more specific α7nAChR ligands as well as more experimental studies and better controlled trials, especially in the field of IBD, are encouraged for a progress in this field.

KEYWORDS:

• α7nAChR
• inflammatory bowel disease
• immune cells
• cytokines
• intracellular pathways

Article highlights

• Review of cholinergic anti-inflammatory effects in inflammatory bowel disease

• Structure, function and expression of α7 nicotinic ACh receptors

• Mechanisms for anti-inflammatory activity of α7 nicotinic ACh receptors

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by the Canadian Institutes of Health Research [grant no. CIHR-143075], Crohn’s and Colitis Canada [grant no. CCC-2015/GHIA], and Bushehr University of Medical Sciences, Bushehr, Iran.