Antiflagellin antibodies recognize the autoantigens Toll-Like Receptor 5 and Pals 1-associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn’s disease

Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

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Tryptophan increases intestinal permeability and decreases intestinal tight junction protein expression in weanling piglets1

Journal of Animal Science ◽

10.2527/jas.2015-9465 ◽

2016 ◽

Vol 94 (suppl_3) ◽

pp. 87-90

Author(s):

X. L. Li ◽

M. Jiang ◽

Z. Ruan ◽

S. M. Mi ◽

X. Wu ◽

...

Keyword(s):

Protein Expression ◽

Tight Junction ◽

Intestinal Permeability ◽

Tight Junction Protein ◽

Tight Junction Protein Expression ◽

Junction Protein

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Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3

International Journal of Molecular Sciences ◽

10.3390/ijms21217824 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7824

Author(s):

Jia-Chen Hu ◽

Christian Bojarski ◽

Federica Branchi ◽

Michael Fromm ◽

Susanne Krug

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Tight Junction ◽

Barrier Function ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Fat Tissue ◽

Jak2 Inhibitor ◽

Junction Protein ◽

Underlying Mechanisms

Crohn’s disease (CD) has an altered intestinal barrier function, yet the underlying mechanisms remain to be disclosed. The tricellular tight junction protein tricellulin is involved in the maintenance of the paracellular macromolecule barrier and features an unchanged expression level in CD but a shifted localization. As angulins are known to regulate the localization of tricellulin, we hypothesized the involvement of angulins in CD. Using human biopsies, we found angulin-1 was downregulated in active CD compared with both controls and CD in remission. In T84 and Caco-2 monolayers, leptin, a cytokine secreted by fat tissue and affected in CD, decreased angulin-1 expression. This effect was completely blocked by STAT3 inhibitors, Stattic and WP1066, but only partially by JAK2 inhibitor AG490. The effect of leptin was also seen at a functional level as we observed in Caco-2 cells an increased permeability for FITC-dextran 4 kDa indicating an impaired barrier against macromolecule uptake. In conclusion, we were able to show that in active CD angulin-1 expression is downregulated, which leads to increased macromolecule permeability and is inducible by leptin via STAT3. This suggests that angulin-1 and leptin secretion are potential targets for intervention in CD to restore the impaired intestinal barrier.

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Interesterified palm oil increases intestinal permeability, promotes bacterial translocation, alters inflammatory parameters and tight-junction protein genic expression in Swiss mice

Food Research International ◽

10.1016/j.foodres.2021.110897 ◽

2021 ◽

pp. 110897

Author(s):

Penélope Lacrísio dos Reis Menta ◽

Maria Emília Rabelo Andrade ◽

Lívia Furquim de Castro ◽

Luísa Martins Trindade ◽

Melissa Tainan Silva Dias ◽

...

Keyword(s):

Tight Junction ◽

Intestinal Permeability ◽

Palm Oil ◽

Bacterial Translocation ◽

Tight Junction Protein ◽

Swiss Mice ◽

Inflammatory Parameters ◽

Junction Protein

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Elevated flagellin-specific immunoglobulins in Crohn's disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00357.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. G403-G406 ◽

Cited By ~ 89

Author(s):

Shanthi V. Sitaraman ◽

Jan-Michael Klapproth ◽

Daniel A. Moore ◽

Carol Landers ◽

Stephan Targan ◽

...

Keyword(s):

Immune Response ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Immune Responses ◽

Acute Inflammation ◽

Adaptive Immune Response ◽

Toll Like Receptor ◽

Adaptive Immune ◽

Specific Antigens ◽

Toll Like Receptor 5

Crohn's disease (CD) is driven by seemingly aberrant immune responses directed toward commensal enteric microflora. However, the specific antigens targeted by this immune response remain largely undefined. Herein, we demonstrate that common enteric flagellins are one such target of the CD-associated immune response. Thus flagellin may not only drive acute inflammation via activation of Toll-like receptor 5-mediated gene expression but may also serve as a target of the adaptive immune response that maintains the chronic inflammation characteristic of CD.

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