Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking?

Abstract

Inflammatory bowel disease (IBD) is characterized by severe gastrointestinal inflammation and results from a complex interplay between genetic and environmental factors. IBD includes two prominent subtypes: Crohn's disease (CD) and ulcerative colitis (UC). One of the main risk factors for the development of CD is cigarette smoking, while UC is rather a disease of ex-smokers. To date, many of the mechanisms underlying the immune imbalance in IBD and the involvement of cigarette smoke (CS) are incompletely understood. Transient receptor potential (TRP) proteins are non-selective cation channels that, upon activation, lead to plasma membrane depolarization and, in general, to Ca²⁺ influx. TRP channels of the ankyrin and vanilloid family, expressed by sensory neurons in the central and enteric nervous systems, have been extensively studied in the context of intestinal inflammation. Moreover, recent advances made on the role of non-neuronal expressed TRP channels shed light on the involvement of epithelial cells in inflammatory processes. This review focuses on how CS may impact TRP channel function in intestinal inflammation. Firstly, we discuss the current knowledge on neuronal TRP channels, known to be linked to IBD, in health, immune homeostasis and intestinal inflammation. Subsequently, we address how TRP channels are activated by CS and its components in other organ systems and also hypothesize on the potential implications for CS-mediated TRP channel activation in gut inflammation.

Animal Inhalation Models to Investigate Modulation of Inflammatory Bowel Diseases

“…Differences between mice and humans at the level of the gut microbiota limit the usefulness of mouse models, relevant to CS, gut microbiota and IBD. However, a few studies using rats and mice were consistent with observations in humans, indicating CS-dependent shifts in gut microbiota compositions [131][132][133]. These observations supported a possible role for CS in shaping the gut microbiome, with potential, though still unknown, consequences for evolution of inflammation-related disorders, such as IBD.…”

Transient Receptor Potential Channels and Inflammatory Bowel Disease

“…Additionally, TRP channels in the GI tract can mediate the crosstalk between the nervous and immune systems by modulating the release of neuropeptides. TRPV1, TRPA1, and TRPV4 are especially often found to colocalize with CGRP and SP (6,14). CGRP, which is generated from the alternative RNA processing of the gene for calcitonin, serves as a potent peptide vasodilator and is involved in the transmission of nociception (15).…”

Review article: impact of cigarette smoking on intestinal inflammation—direct and indirect mechanisms

“…The gut is extensively innervated, and its function is controlled by both the autonomous nervous system and its own enteric or intrinsic nervous system 94 . Intestinal epithelial cells and neurons of the intrinsic nervous system have similar expression patterns of specific sensory transient receptor potential channels; including TRPA1, TRPV1 and TRPV4.…”