Upregulation of the Transient Receptor Potential Ankyrin 1 Ion Channel in the Inflamed Human and Mouse Colon and Its Protective Roles

Kun, József; Szitter, István; Kemény, Ágnes; Perkecz, Anikó; Kereskai, László; Pohóczky, Krisztina; Vincze, Áron; Gódi, Szilárd; Szabó, Imre; Szolcsányi, Janós; Pintér, Erika; Helyes, Zsuzsanna

doi:10.1371/journal.pone.0108164

Cited by 115 publications

(137 citation statements)

References 96 publications

(98 reference statements)

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…1), e.g. the serous acinar and ductal cells of the human submandibular gland, the gastrin and parietal cells of the stomach, the epithelial cells of the esophagus, stomach and ileum and the enteroendocrine cells, macrophages, CD4+ T cells and CD45+ cells in the gastrointestinal tract [53,60,62,63,64,65,66,67,68,69,70,71]. …”

Section: Localization Of Trp Channels In the Gutmentioning

confidence: 99%

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

Allais

Smet²,

Verschuere³

et al. 2016

Pathobiology

View full text Add to dashboard Cite

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.

show abstract

Section: Localization Of Trp Channels In the Gutmentioning

confidence: 99%

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

Allais

Smet²,

Verschuere³

et al. 2016

Pathobiology

View full text Add to dashboard Cite

show abstract

“…Recently, it has been reported that TRPA1 as well as TRPM7 is functionally expressed on macrophages [7]. In addition, the specific inhibitors of TRPM7 prevent the polarization of macrophages towards the anti-inflammatory M2…”

Section: Discussionmentioning

confidence: 99%

“…Of proinflammatory mediators initially induced by surgical incision, interleukin (IL)-1 plays a critical host defense role against S. aureus by enhancing neutrophil recruitment [6]. Proinflammatory mediators such as IL-1 and tumor necrosis factor (TNF) were also shown to be upregulated in a colitis model of TRPA1 −/− mice, independent of toll-like receptors [7]. In addition, oxygen partial pressure was found to regulate TRPA1 activation in sensory neurons [8], suggesting that neuronal TRPA1 regulates the changes in the local inflammatory responses dependent on the changes in tissue environ-ment that are likely to occur after a surgical procedure.…”

Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential Ankyrin 1 Ion Channel Facilitates Acute Inflammation Induced by Surgical Incision in Mice

Hasegawa-Moriyama¹,

Mukaihara²,

Yamada³

et al. 2017

OJAnes

View full text Add to dashboard Cite

Background: Transient receptor potential ankyrin (TRPA) 1 is known as a peripheral initiator of acute inflammation and hyperalgesia. However, its role in the facilitation of innate immune responses followed by resolution of the inflammation triggered by a surgical incision has not been fully investigated. Therefore, we evaluated the mechanism by which TRPA1 regulates the inflammatory responses mainly facilitated by neutrophils and macrophages in the early course of wound repair after an incision. Methods: Plantar incision was performed in wild-type and TRPA1 −/− mice. The infiltration of polymorphonuclear neutrophils, macrophage phenotype, and induction of inflammatory mediators were assessed for 7 days postoperatively. Results: TRPA1 −/− mice exhibited decreased infiltration of polymorphonuclear neutrophilscompared with wild-type mice on day 1. Consistently, the influx of F4/80 + iNOS + proinflammatory M1 macrophages to incised sites was markedly decreased on day 2. Similarly, F4/80 + CD206 + M2 macrophages, which regulate the resolution of inflammation and promote wound healing in the later phase of acute inflammation, were significantly decreased in TRPA1 −/− compared with those in wild-type mice on day 7. In addition, the induction of heme oxygenase-1, which promotes wound healing by switching phenotype of macrophages, was decreased in the early phase of acute inflammation, whereas the expression of proinflammatory mediators such as tumor necrosis factor and cyclooxygenase-2, and 15-lipoxygenase, which are involved in the resolution of inflammation was increased in the late phase in TRPA1 135facilitate the acute inflammatory process, leading to the promotion of macrophage-mediated resolution of inflammation and wound repair after a surgical incision.

show abstract

“…A marked upregulation of PACAP (and of VIP) mRNA expression was shown in TRPA1 (transient receptor potential Ankyrin type 1) KO mice, while this was not observed in wild type controls [ 84 ]. Expression levels of VPAC2 and PAC1R mRNA were not altered, whereas that of VPAC1 was downregulated in TRPA1 KO mice 10 days following colitis induction [ 84 ]. An earlier study revealed that mice lacking the TRPV-1 (transient receptor potential cation channel subfamily V member 1) receptor exhibit a defect in PACAP expression.…”

Section: Effects Of Pacap In Large Intestinal Infl Ammationmentioning

confidence: 97%

“…Changes in PACAP and receptor expression were also demonstrated in dextran sodium sulfate (DSS)-induced colitis of mice. A marked upregulation of PACAP (and of VIP) mRNA expression was shown in TRPA1 (transient receptor potential Ankyrin type 1) KO mice, while this was not observed in wild type controls [ 84 ]. Expression levels of VPAC2 and PAC1R mRNA were not altered, whereas that of VPAC1 was downregulated in TRPA1 KO mice 10 days following colitis induction [ 84 ].…”

Section: Effects Of Pacap In Large Intestinal Infl Ammationmentioning

confidence: 99%

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Horváth

Illés

Heimesaat

et al. 2016

Current Topics in Neurotoxicity

View full text Add to dashboard Cite

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia-reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine.

show abstract

Upregulation of the Transient Receptor Potential Ankyrin 1 Ion Channel in the Inflamed Human and Mouse Colon and Its Protective Roles

Cited by 115 publications

References 96 publications

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

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

Transient Receptor Potential Ankyrin 1 Ion Channel Facilitates Acute Inflammation Induced by Surgical Incision in Mice

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Contact Info

Product

Resources

About