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Open AccessArticle

Nutritional and Pharmacological Targeting of the Calcium-Sensing Receptor Influences Chemically Induced Colitis in Mice

1
Center of Pathophysiology Infectiology and Immunology, Medical University of Vienna, Pathophysiology and Allergy Research, Währinger Gürtel, 18-20, 1090 Vienna, Austria
2
Pathologie Überlingen, 88662 Überlingen, Germany
3
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, CF10 3NB Cardiff, UK
4
Department of Chemistry, College of Science, Swansea University, SA2 8PP Swansea, UK
5
Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2019, 11(12), 3072; https://doi.org/10.3390/nu11123072
Received: 21 November 2019 / Revised: 12 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019
(This article belongs to the Special Issue Immunomodulation and Nutrition)
The calcium-sensing receptor (CaSR) is the main regulator of extracellular Ca2+ homeostasis. It has diverse functions in different tissues, including the intestines. Intestine-specific knockout of the CaSR renders mice more susceptible to dextran sulphate sodium (DSS)-induced colitis. To test our hypothesis that the CaSR reduces intestinal inflammation, we assessed the effects of nutritional and pharmacological agonists of the CaSR in a colitis model. We treated female Balb/C mice with dietary calcium and protein (nutritional agonists of the CaSR) or pharmacological CaSR modulators (the agonists cinacalcet and GSK3004774, and the antagonist NPS-2143; 10 mg/kg), then induced colitis with DSS. The high-protein diet had a strong pro-inflammatory effect—it shortened the colons (5.3 ± 0.1 cm vs. 6.1 ± 0.2 cm normal diet, p < 0.05), lowered mucin expression and upregulated pro-inflammatory cytokines, such as interferon-γ, (4.2-fold, p < 0.05) compared with the normal diet. Cinacalcet reduced mucin expression, which coincided with an increase in tumor necrosis factor-α (4.4-fold, p < 0.05) and IL-6 (4.9-fold, p < 0.05) in the plasma, compared with vehicle. The CaSR antagonist, NPS-2143, significantly reduced the cumulative inflammation score compared with the vehicle control (35.3 ± 19.1 vs. 21.9 ± 14.3 area under the curve, p < 0.05) and reduced infiltration of inflammatory cells. While dietary modulation of the CaSR had no beneficial effects, pharmacological inhibition of the CaSR may have the potential of a novel add-on therapy in the treatment of inflammatory bowel diseases. View Full-Text
Keywords: IBD; colitis; inflammation; calcium; mucin IBD; colitis; inflammation; calcium; mucin
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MDPI and ACS Style

Elajnaf, T.; Iamartino, L.; Mesteri, I.; Müller, C.; Bassetto, M.; Manhardt, T.; Baumgartner-Parzer, S.; Kallay, E.; Schepelmann, M. Nutritional and Pharmacological Targeting of the Calcium-Sensing Receptor Influences Chemically Induced Colitis in Mice. Nutrients 2019, 11, 3072. https://doi.org/10.3390/nu11123072

AMA Style

Elajnaf T, Iamartino L, Mesteri I, Müller C, Bassetto M, Manhardt T, Baumgartner-Parzer S, Kallay E, Schepelmann M. Nutritional and Pharmacological Targeting of the Calcium-Sensing Receptor Influences Chemically Induced Colitis in Mice. Nutrients. 2019; 11(12):3072. https://doi.org/10.3390/nu11123072

Chicago/Turabian Style

Elajnaf, Taha; Iamartino, Luca; Mesteri, Ildiko; Müller, Christian; Bassetto, Marcella; Manhardt, Teresa; Baumgartner-Parzer, Sabina; Kallay, Enikö; Schepelmann, Martin. 2019. "Nutritional and Pharmacological Targeting of the Calcium-Sensing Receptor Influences Chemically Induced Colitis in Mice" Nutrients 11, no. 12: 3072. https://doi.org/10.3390/nu11123072

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