Interferon-γ and tumor necrosis factor-α disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction

Li, Qiurong; Zhang, Qiang; Wang, Meng; Zhao, Sumin; Ma, Jian; Luo, Nan; Li, Ning; Li, Yousheng; Gao, Xu; Li, Jieshou

doi:10.1016/j.clim.2007.08.017

Cited by 105 publications

(94 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent epidemiologic evidence, however, suggests a refluxindependent mechanism by which central obesity may increase the risk of esophageal inflammation and neoplasia. 21 Indeed, with stratification of groups by acid reflux and central obesity status that enabled an accurate and objective assessment of the effects of central obesity independent of acid reflux, we demonstrated that ICSD occurs in centrally obese patients in the absence of documented GER. Thus, disruption of the esophageal epithelial barrier may be an underlying mechanism by which increased visceral abdominal fat increases the susceptibility of the esophageal epithelium to reflux-mediated injury and inflammation that potentiates the development of metaplasia and neoplasia.…”

Section: Discussionmentioning

confidence: 99%

Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium

et al. 2016

View full text Add to dashboard Cite

Background: While central obesity increases gastroesophageal reflux (GER) by mechanically disrupting the anti-reflux barrier, limited data exist on pathways by which central obesity may potentiate esophageal injury by non-mechanical means. Obesity has been associated with an impaired epithelial intestinal barrier. Objective: We aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD). Methods: The ICSD was measured using electron microscopy in esophageal biopsies from individuals who underwent ambulatory pH monitoring and endoscopy. Anthropometric measurements were obtained on all participants. Participants were classified into four groups: with and without central obesity and reflux. Results: Sixteen individuals were studied with four in each study group. The mean ICSD was almost three-fold greater (p < 0.001) in the group with central obesity without reflux, compared to controls without central obesity and reflux. It was also comparable to the ICSD in groups with acid reflux only and those with both reflux and central obesity. Conclusions: There is evidence of esophageal squamous ICSD increase in individuals with central obesity who do not have evidence of acid and nonacid reflux on ambulatory pH monitoring. This may reflect a mechanism by which central obesity potentiates reflux-induced esophageal injury and inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Displacement of the TJ protein junction adhesion molecule-A from raft fractions has been noted in intestinal epithelial cells exposed to a combination of the proinflammatory cytokines IFN-␥ and TNF-␣ (6), and the same cytokines have been shown to alter the lipid composition of membrane microdomains (22). Therefore our study investigated the relationship between raft integrity, barrier function, and an inflammatory microenvironment using three complementary models: intestinal epithelial cells primed with a proinflammatory barrier-disrupting cytokine, mouse models of colitis, and human intestinal IBD biopsies.…”

mentioning

confidence: 99%

“…This study reports for the first time that lipid raft disruption is a feature of all three inflammatory microenvironments and provides novel evidence that raft disruption precedes the loss of barrier function in colitic mice. Given that rafts are sensitive to alterations in lipid balance (22) and that dietary modulation of lipid balance reportedly influences the course of human IBD (55), this may merit further investigation into the role of lipid rafts in modifying early-stage inflammatory events associated with IBD.…”

mentioning

confidence: 99%

Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier

Bowie

Donatello

Lyes

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…The production of proinflammatory cytokines and chemokines is enhanced in epithelia during mucosal inflammation, and IFN-g is one of the most prominent proinflammatory cytokines that profoundly affects epithelial cells. Elevated IFN-g enhances paracellular permeability via the displacement of selected tight junction proteins in membrane microdomains but in a manner that does not involve apoptosis (20,21). Moreover, IFNg inhibits enterocyte migration by reversibly displacing connexin43 from lipid rafts, which leads to the blocking of interenterocyte gap junction communication and epithelial restitution after ulcerative injury (22,23).…”

mentioning

confidence: 99%

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Hun

Choi

Kim

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Although the activation of B cells in the gastrointestinal tract is of great importance in the context of immunity to pathogens and mucosal inflammatory diseases, little is known about the mechanisms responsible for the local activation of B cells in the subepithelial area of the intestine. Epithelium-derived BAFF is the major modulator of B cell development and Ig class switching. The present study was performed to address the molecular mechanism of BAFF expression in gut epithelial cells in the presence of proinflammatory stimuli. Inflammation-induced BAFF expression in mucosal epithelial cells might be responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Although BAFF was marginally expressed in unstimulated epithelial cells, BAFF mRNA was significantly upregulated by proinflammatory IFN-γ. Furthermore, IFN-γ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-γ–activated JAK/STAT signal transduction and subsequent BAFF induction in gut epithelial cells. Ribosomal insults led to the superinduction of SOCS3 by enhancing its mRNA stability via HuR RNA-binding protein. Upregulated SOCS3 then contributed to the blocking of the JAK/STAT-linked signal, which mediated BAFF suppression by ribosomal stress. All of these findings show that ribosomal stress–induced SOCS3 plays a novel regulatory role in epithelial BAFF production, suggesting that epithelial ribosomal dysfunction in association with SOCS3 may be a promising therapeutic point in BAFF-associated human mucosal diseases.

show abstract

Interferon-γ and tumor necrosis factor-α disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction

Cited by 105 publications

References 31 publications

Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium

Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium

Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Contact Info

Product

Resources

About