Opposing Regulation of the Tight Junction Protein Claudin-2 by Interferon-γ and Interleukin-4

Wisner, Douglas; Harris, Leonard; Green, Cecelia L.; Poritz, Lisa S.

doi:10.1016/j.jss.2007.03.059

Cited by 46 publications

(22 citation statements)

References 36 publications

(48 reference statements)

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“…48 IL-6 and IL-4 correlate to increased permeability potentially due to the induction of pore-forming claudin-2 expression. 49,50 Furthermore, all of them were restored in both L. rhamnosus and F. prausnitzii-treated mice.…”

Section: Discussionmentioning

confidence: 95%

Lactobacillus rhamnosusCNCM I-3690 and the commensal bacteriumFaecalibacterium prausnitziiA2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice

Laval¹,

Martin²,

Natividad³

et al. 2015

Gut Microbes

155

108

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Impaired gut barrier function has been reported in a wide range of diseases and syndromes and in some functional gastrointestinal disorders. In addition, there is increasing evidence that suggests the gut microbiota tightly regulates gut barrier function and recent studies demonstrate that probiotic bacteria can enhance barrier integrity. Here, we aimed to investigate the effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal barrier function. In vitro results using a Caco-2 monolayer cells stimulated with TNF-α confirmed the anti-inflammatory nature of the strain CNCM I-3690 and pointed out a putative role for the protection of the epithelial function. Next, we tested the protective effects of L. rhamnosus CNCM I-3690 in a mouse model of increased colonic permeability. Most importantly, we compared its performance to that of the well-known beneficial human commensal bacterium Faecalibacterium prauznitzii A2-165. Increased colonic permeability was normalized by both strains to a similar degree. Modulation of apical tight junction proteins expression was then analyzed to decipher the mechanism underlying this effect. We showed that CNCM I-3690 partially restored the function of the intestinal barrier and increased the levels of tight junction proteins Occludin and E-cadherin. The results indicate L. rhamnosus CNCM I-3690 is as effective as the commensal anti-inflammatory bacterium F. prausnitzii to treat functional barrier abnormalities.

show abstract

Section: Discussionmentioning

confidence: 95%

Lactobacillus rhamnosusCNCM I-3690 and the commensal bacteriumFaecalibacterium prausnitziiA2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice

Laval¹,

Martin²,

Natividad³

et al. 2015

Gut Microbes

155

108

View full text Add to dashboard Cite

show abstract

“…IFN-γ selectively increases epithelial permeability to large molecules by direct alteration of TJP assembly [36], [37]. STAT-1 is an important signaling molecule for IFN-γ; and STAT1 activation in IECs leads to downstream proinflammatory gene expression, predisposing IECs to injury [38], [39].…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of pore-forming claudin 2 leads to altered tight junction structure and pronounced barrier dysfunction in mild to moderately active Crohn's disease [46]. Conversely, reduced levels of claudin-2 or JAM-A may also lead to disrupted barrier function [36]. Therefore, GCC signaling may be relevant to regulation of intestinal barrier function directly through interacting with TJPs.…”

Section: Discussionmentioning

confidence: 99%

Loss of Guanylyl Cyclase C (GCC) Signaling Leads to Dysfunctional Intestinal Barrier

et al. 2011

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BackgroundGuanylyl Cyclase C (GCC) signaling via uroguanylin (UGN) and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function.Methodology/Principal FindingsParacellular permeability of intestinal segments was assessed in wild type (WT) and GCC deficient (GCC−/−) mice with and without lipopolysaccharide (LPS) challenge, as well as in UGN deficient (UGN−/−) mice. IFNγ and myosin light chain kinase (MLCK) levels were determined by real time PCR. Expression of tight junction proteins (TJPs), phosphorylation of myosin II regulatory light chain (MLC), and STAT1 activation were examined in intestinal epithelial cells (IECs) and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi). We found that intestinal permeability was increased in GCC−/− and UGN−/− mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC−/− mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC−/− and UGN−/− mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability.Conclusions/SignificanceGCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury.

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“…77 Although potential changes in the expression of claudin proteins were not reported, all 3 cytokines are known to have significant effects on TJ protein expression, including the regulation of claudin-2. 30,32,34,78 A more direct link between claudin-2 and the induction of colitis is found in SAMP1/YitFc mice, which show an increase in claudin-2 expression and intestinal permeability that precedes the onset of a spontaneous Crohn's disease-like ileitis. 79 …”

Section: Crohn's Diseasementioning

confidence: 99%

Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation

et al. 2015

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Opposing Regulation of the Tight Junction Protein Claudin-2 by Interferon-γ and Interleukin-4

Cited by 46 publications

References 36 publications

Lactobacillus rhamnosusCNCM I-3690 and the commensal bacteriumFaecalibacterium prausnitziiA2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice

Lactobacillus rhamnosusCNCM I-3690 and the commensal bacteriumFaecalibacterium prausnitziiA2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice

Loss of Guanylyl Cyclase C (GCC) Signaling Leads to Dysfunctional Intestinal Barrier

Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation

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