Curcumin Mitigates Immune-Induced Epithelial Barrier Dysfunction by Campylobacter jejuni
by
Fábia Daniela Lobo de Sá 1
, Eduard Butkevych 1, Praveen Kumar Nattramilarasu 1, Anja Fromm 1, Soraya Mousavi 2, Verena Moos 3, Julia C. Golz 4, Kerstin Stingl 4, Sophie Kittler 5, Diana Seinige 5, Corinna Kehrenberg 6, Markus M. Heimesaat 2, Stefan Bereswill 2, Jörg-Dieter Schulzke 1,* and Roland Bücker 1
Fábia Daniela Lobo de Sá 1, Eduard Butkevych 1, Praveen Kumar Nattramilarasu 1, Anja Fromm 1, Soraya Mousavi 2, Verena Moos 3, Julia C. Golz 4, Kerstin Stingl 4, Sophie Kittler 5, Diana Seinige 5, Corinna Kehrenberg 6, Markus M. Heimesaat 2, Stefan Bereswill 2, Jörg-Dieter Schulzke 1,* and Roland Bücker 1
1
Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité–Universitätsmedizin Berlin, 12203 Berlin, Germany
2
Institute of Microbiology, Infectious Diseases and Immunology, Charité–Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany
3
Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité–Universitätsmedizin Berlin, 12203 Berlin, Germany
4
German Federal Institute for Risk Assessment (BfR), Department of Biological Safety, National Reference Laboratory for Campylobacter, 12277 Berlin, Germany
5
University of Veterinary Medicine Hannover, Research Center for Emerging Infections and Zoonoses, 30559 Hannover, Germany
6
Institute for Veterinary Food Science, Justus-Liebig-University, 35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(19), 4830; https://doi.org/10.3390/ijms20194830
Received: 5 August 2019 / Revised: 19 September 2019 / Accepted: 26 September 2019 / Published: 28 September 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Campylobacter jejuni (C. jejuni) is the most common cause of foodborne gastroenteritis worldwide. The bacteria induce diarrhea and inflammation by invading the intestinal epithelium. Curcumin is a natural polyphenol from turmeric rhizome of Curcuma longa, a medical plant, and is commonly used in curry powder. The aim of this study was the investigation of the protective effects of curcumin against immune-induced epithelial barrier dysfunction in C. jejuni infection. The indirect C. jejuni-induced barrier defects and its protection by curcumin were analyzed in co-cultures with HT-29/B6-GR/MR epithelial cells together with differentiated THP-1 immune cells. Electrophysiological measurements revealed a reduction in transepithelial electrical resistance (TER) in infected co-cultures. An increase in fluorescein (332 Da) permeability in co-cultures as well as in the germ-free IL-10−/− mouse model after C. jejuni infection was shown. Curcumin treatment attenuated the C. jejuni-induced increase in fluorescein permeability in both models. Moreover, apoptosis induction, tight junction redistribution, and an increased inflammatory response—represented by TNF-α, IL-1β, and IL-6 secretion—was observed in co-cultures after infection and reversed by curcumin. In conclusion, curcumin protects against indirect C. jejuni-triggered immune-induced barrier defects and might be a therapeutic and protective agent in patients.
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Keywords:
Campylobacter jejuni; curcumin; tight junction; claudin; apoptosis; co-culture; mouse colon; cytokines; TNF; NFκB
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MDPI and ACS Style
Lobo de Sá, F.D.; Butkevych, E.; Nattramilarasu, P.K.; Fromm, A.; Mousavi, S.; Moos, V.; Golz, J.C.; Stingl, K.; Kittler, S.; Seinige, D.; Kehrenberg, C.; Heimesaat, M.M.; Bereswill, S.; Schulzke, J.-D.; Bücker, R. Curcumin Mitigates Immune-Induced Epithelial Barrier Dysfunction by Campylobacter jejuni. Int. J. Mol. Sci. 2019, 20, 4830.
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