Curcumin Mitigates Immune-Induced Epithelial Barrier Dysfunction by Campylobacter jejuni

Sá, Fábia Daniela Lobo de; Butkevych, Eduard; Nattramilarasu, Praveen Kumar; Fromm, Anja; Mousavi, Soraya; Moos, Verena; Golz, Julia C.; Stingl, Kerstin; Kittler, Sophie; Seinige, Diana; Kehrenberg, Corinna; Heimesaat, Markus M.; Bereswill, Stefan; Schulzke, Jörg–Dieter; Bücker, Roland

doi:10.3390/ijms20194830

Cited by 39 publications

(55 citation statements)

References 52 publications

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“…Since then, abiotic IL-10 −/− mouse model has been successfully employed in many studies [48][49][50][51]. In recent studies, the abiotic IL-10 −/− mouse model was also used to determine the barrier protective and anti-inflammatory effects on C. jejuni infection using curcumin or vitamin D [52,53].…”

Section: Discussionmentioning

confidence: 99%

Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption

Nattramilarasu

Bücker

Sá

et al. 2020

IJMS

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The epithelial sodium channel (ENaC) can increase the colonic absorptive capacity for salt and water. Campylobacter concisus is a common pathogenic epsilonproteobacterium, causing enteritis and diarrhea. It can induce barrier dysfunction in the intestine, but its influence on intestinal transport function is still unknown. Therefore, our study aimed to characterize C. concisus effects on ENaC using the HT-29/B6-GR/MR (epithelial cell line HT-29/B6 transfected with glucocorticoid and mineralocorticoid receptors) cell model and mouse colon. In Ussing chambers, C. concisus infection inhibited ENaC-dependent Na+ transport as indicated by a reduction in amiloride-sensitive short circuit current (−55%, n = 15, p < 0.001). This occurred via down-regulation of β- and γ-ENaC mRNA expression and ENaC ubiquitination due to extracellular signal-regulated kinase (ERK)1/2 activation, predicted by Ingenuity Pathway Analysis (IPA). In parallel, C. concisus reduced the expression of the sealing tight junction (TJ) protein claudin-8 and induced claudin-8 redistribution off the TJ domain of the enterocytes, which facilitates the back leakage of Na+ ions into the intestinal lumen. In conclusion, C. concisus caused ENaC dysfunction via interleukin-32-regulated ERK1/2, as well as claudin-8-dependent barrier dysfunction—both of which contribute to Na+ malabsorption and diarrhea.

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Section: Discussionmentioning

confidence: 99%

Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption

Nattramilarasu

Bücker

Sá

et al. 2020

IJMS

Self Cite

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“…Furthermore, the increased concentrations of pro-inflammatory cytokines such as TNF-α, IL.-1β and IL-6 in C. jejuni infected co-cultures were down-regulated after curcumin treatment [99]. These results indicate that curcumin in competition to TLR-4 binding antagonized local and systemic inflammatory responses triggered by bacterial LPS/LOS [99,100]. Moreover, it has been reported that the competition between curcumin and LPS/LOS to bind TLR-4 inhibited the MyD88-dependent pathway [101].…”

Section: Activation Of Tlr-4 Signaling By C Jejuni Lipooligosaccharimentioning

confidence: 95%

“…Interestingly, there are several natural plant products such as curcumin derived from Curcuma longa acting as highly effective TLR-4 antagonists by non-activate binding leading to competitive inhibition of LPS/LOS functions [98]. Recently, it has been demonstrated that apoptosis induction, tight junction redistribution, and increased inflammatory responses upon C. jejuni infection were down-regulated after curcumin treatment in a co-culture model of human colon epithelial cells HT-29/B6-GR/MR and immune THP-1 cells [99]. Additionally, curcumin could effectively ameliorate the campylobacteriosis symptoms including apoptosis, T-cell mediated inflammatory responses and colonic barrier dysfunction, observed in C. jejuni infected IL10 −/− mice [99].…”

Section: Activation Of Tlr-4 Signaling By C Jejuni Lipooligosaccharimentioning

confidence: 99%

“…Recently, it has been demonstrated that apoptosis induction, tight junction redistribution, and increased inflammatory responses upon C. jejuni infection were down-regulated after curcumin treatment in a co-culture model of human colon epithelial cells HT-29/B6-GR/MR and immune THP-1 cells [99]. Additionally, curcumin could effectively ameliorate the campylobacteriosis symptoms including apoptosis, T-cell mediated inflammatory responses and colonic barrier dysfunction, observed in C. jejuni infected IL10 −/− mice [99]. Furthermore, the increased concentrations of pro-inflammatory cytokines such as TNF-α, IL.-1β and IL-6 in C. jejuni infected co-cultures were down-regulated after curcumin treatment [99].…”

Section: Activation Of Tlr-4 Signaling By C Jejuni Lipooligosaccharimentioning

confidence: 99%

“…Additionally, curcumin could effectively ameliorate the campylobacteriosis symptoms including apoptosis, T-cell mediated inflammatory responses and colonic barrier dysfunction, observed in C. jejuni infected IL10 −/− mice [99]. Furthermore, the increased concentrations of pro-inflammatory cytokines such as TNF-α, IL.-1β and IL-6 in C. jejuni infected co-cultures were down-regulated after curcumin treatment [99]. These results indicate that curcumin in competition to TLR-4 binding antagonized local and systemic inflammatory responses triggered by bacterial LPS/LOS [99,100].…”

Section: Activation Of Tlr-4 Signaling By C Jejuni Lipooligosaccharimentioning

confidence: 99%

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Novel Clinical Campylobacter jejuni Infection Models Based on Sensitization of Mice to Lipooligosaccharide, a Major Bacterial Factor Triggering Innate Immune Responses in Human Campylobacteriosis

2020

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: Human Campylobacter jejuni infections inducing campylobacteriosis including post-infectious sequelae such as Guillain-Barré syndrome and reactive arthritis are rising worldwide and progress into a global burden of high socioeconomic impact. Intestinal immunopathology underlying campylobacteriosis is a classical response of the innate immune system characterized by the accumulation of neutrophils and macrophages which cause tissue destruction, barrier defects and malabsorption leading to bloody diarrhea. Clinical studies revealed that enteritis and post-infectious morbidities of human C. jejuni infections are strongly dependent on the structure of pathogenic lipooligosaccharides (LOS) triggering the innate immune system via Toll-like-receptor (TLR)-4 signaling. Compared to humans, mice display an approximately 10,000 times weaker TLR-4 response and a pronounced colonization resistance (CR) against C. jejuni maintained by the murine gut microbiota. In consequence, investigations of campylobacteriosis have been hampered by the lack of experimental animal models. We here summarize recent progress made in the development of murine C. jejuni infection models that are based on the abolishment of CR by modulating the murine gut microbiota and by sensitization of mice to LOS. These advances support the major role of LOS driven innate immunity in pathogenesis of campylobacteriosis including post-infectious autoimmune diseases and promote the preclinical evaluation of novel pharmaceutical strategies for prophylaxis and treatment.

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Dietary phytochemicals modulate intestinal epithelial barrier dysfunction and autoimmune diseases

et al. 2021

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The intestinal epithelium acts as a key defensive barrier that protects internal organs from the detrimental gut environment. The homeostasis of the gut epithelium may be altered by environmental conditions and exogenous pathogens that can impair the integrity of the gut barrier, leading to immune response associated with low‐grade systemic inflammation, a known contributor to metabolic and inflammatory diseases. Autoimmune diseases (ADs) are a collection of abnormalities of the immune system, in which the immune system of an individual acts against healthy organs or systems, due to a failure in antigenic recognition. Hence, this review aims to focus on modulators of intestinal epithelial barrier dysfunction with effects on autoimmune disorders. All data on dietary phytochemicals and their impact on the modulation of the intestinal epithelium barrier and various ADs were collected from electronic searches of library databases (PubMed, Science Direct, and Google Scholar). An electronic search was conducted using PubMed, Science Direct, and Google Scholar by finding the keywords “phytochemicals” AND “bioactive compounds” AND “flavonoids” AND “polyphenols” OR “intestinal epithelium barrier” OR “autoimmune diseases” OR “inflammatory diseases” in “Title/Abstract/Keywords,” with the date from January 2011 to December 2020, to identify all published studies (in vitro, in vivo, clinical, and case‐control) that have investigated the connection between dietary phytochemicals and their various beneficial effects. Dietary phytochemicals are promising key modulators, stabilizing the integrity of the intestinal barrier and attenuating the progression of ADs. Health‐modulatory information was gathered and orchestrated in a suitable place in this review.

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Curcumin Mitigates Immune-Induced Epithelial Barrier Dysfunction by Campylobacter jejuni

Cited by 39 publications

References 52 publications

Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption

Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption

Novel Clinical Campylobacter jejuni Infection Models Based on Sensitization of Mice to Lipooligosaccharide, a Major Bacterial Factor Triggering Innate Immune Responses in Human Campylobacteriosis

Dietary phytochemicals modulate intestinal epithelial barrier dysfunction and autoimmune diseases

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