Basic—Alimentary TractTransient Receptor Potential Vanilloid 4 Activated Inflammatory Signals by Intestinal Epithelial Cells and Colitis in Mice
Section snippets
Cell Culture
T84 human intestinal epithelial cells (CCL-248; American Type Culture Collection, Manassas, VA) were cultured in a mixture of Dulbecco's modified Eagle medium and Ham's F-12 (D6421; Sigma, Saint Quentin Fallavier, France) supplemented with 5% heat-inactivated fetal bovine serum, 100 μg/mL streptomycin, 100 U/mL penicillin, and 2 mmol/L l-glutamine (Invitrogen, Cergy Pontoise, France). Caco-2 human intestinal epithelial cells (HTB-37; American Type Culture Collection) were grown in Dulbecco's
TRPV4 Expression in the Gut
As seen in Figure 1, cytokeratin 18 (in red), a type I intermediate filament protein widely expressed in epithelial cells, colocalized with TRPV4 (in green) in human colonic resections from non-IBD patients (controls) or in tissues from patients with IBD (both Crohn's disease [CD] and ulcerative colitis [UC]). A strong signal for TRPV4 immunostaining was detected in cytokeratin 18–positive epithelial cells (Figure 1A). Using a marker of calcium binding proteins that are localized in the
Discussion
Our study provides evidence for a proinflammatory role of the calcium channel TRPV4 in the intestine and more particularly on intestinal epithelial cells. We identified TRPV4 as a previously unknown mediator of epithelial cell biology, raising evidence that its activation alerts innate immunity.
TRPV4 is not only detected in mouse colonic tissues and human intestinal cell lines but also is strongly expressed in human colonic tissues both from controls (non-IBD patients) and patients with IBD. We
Acknowledgments
The authors thank Dr Alexandre De Nadai Souza, Dr André Buret, Dr Daniela Balz-Hara, Dr Gilles Dietrich, and Tamia Lapointe for technical assistance; the IFR-150 core facilities for microscopy and histopathology; and Dr Nigel Bunnett and Dr Graham Cottrell for providing HEK cells expressing TRPV4.
References (27)
- et al.
Inflammatory bowel disease: the >role of environmental factors
Autoimmun Rev
(2004) - et al.
Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis
Gastroenterology
(2009) - et al.
Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives
J Biol Chem
(2002) - et al.
Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2
Am J Pathol
(2002) - et al.
Therapeutic effects of four strains of probiotics on experimental colitis in mice
World J Gastroenterol
(2009) - et al.
Identification of 5,6-trans-epoxyeicosatrienoic acid in the phospholipids of red blood cells
J Biol Chem
(2004) - et al.
Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-1 activation
Exp Cell Res
(2002) - et al.
Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione
Gastroenterology
(2007) - et al.
Permeation and selectivity of TRP channels
Annu Rev Physiol
(2006) - et al.
TRPV4 calcium entry channel: a paradigm for gating diversity
Am J Physiol Cell Physiol
(2004)
Vanilloid transient receptor potential cation channels: an overview
Curr Pharm Des
Transient receptor potential vanilloid-4 has a major role in visceral hypersensitivity symptoms
Gastroenterology
Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study
J Med Chem
Cited by (113)
Non-electrophysiological techniques targeting transient receptor potential (TRP) gene of gastrointestinal tract
2024, International Journal of Biological MacromoleculesChicken embryo thermal manipulation alleviates postnatal heat stress-induced jejunal inflammation by inhibiting Transient Receptor Potential V4
2023, Ecotoxicology and Environmental SafetyExpression and functions of transient receptor potential channels in liver diseases
2023, Acta Pharmaceutica Sinica BTRP channels in inflammatory bowel disease: Potential therapeutic targets
2022, Biochemical PharmacologyPPARGC1A affects inflammatory responses in photodynamic therapy (PDT)-treated inflammatory bowel disease (IBD)
2022, Biochemical PharmacologyCapsaicin inhibits intestinal Cl<sup>-</sup> secretion and promotes Na<sup>+</sup> absorption by blocking TRPV4 channels in healthy and colitic mice
2022, Journal of Biological ChemistryCitation Excerpt :Finally, it is known that the expression and activity of TRPV4 are enhanced with the reduced Na+ absorption but increased Cl- secretion in UC, leading to colitis diarrhea. Therefore, it has been established that TRPV4 channels activate inflammatory signals by IECs and colitis in humans and mice (17–19). Our findings are in line with the previous notion that small numbers of TRPV4 channels lead to local Ca2+ increase that may play physiological roles, but excessive activation of TRPV4 channels lead to rapid global Ca2+ overload that may cause pathological disorders (27).
Conflicts of interest The authors disclose no conflicts.
Funding N.V. is supported by grants from the Fondation Bettencourt-Schueller, INSERM-AVENIR, Agence Nationale pour la Recherche, Fondation pour la Recherche Medicale, and Fondation Schlumberger.