Intestinal permeability in humans is increased after radiation therapy

Nejdfors, Pernilla; Ekelund, Mats; Weström, Björn; Wïllén, Roger; Jeppsson, Bengt

doi:10.1007/bf02236743

Cited by 82 publications

(52 citation statements)

References 25 publications

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“…Intestinal permeability defects are associated with several intestinal diseases such as IBD, cancer, radiation injury, enterocolitis, and Celiac disease (57)(58)(59)(60)(61)(62). Inflammatory molecules are classically thought to contribute to defects in permeability and exacerbation of disease (63,64).…”

Section: Discussionmentioning

confidence: 99%

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

Vongsa

Zimmerman

Dwinell

2009

Journal of Biological Chemistry

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Intestinal inflammation is exacerbated by defects in the epithelial barrier and subsequent infiltration of microbes and toxins into the underlying mucosa. Production of chemokines and antimicrobial peptides by an intact epithelium provide the first line of defense against invading organisms. In addition to its antimicrobial actions, human beta defensin-2 (HBD2) may also stimulate the migration of dendritic cells through binding the chemokine receptor CCR6. As human colonic epithelium expresses CCR6, we investigated the potential of HBD2 to stimulate intestinal epithelial migration. Using polarized human intestinal Caco2 and T84 cells and non-transformed IEC6 cells, HBD2 was equipotent to CCL20 in stimulating migration. Neutralizing antibodies confirmed HBD2 and CCL20 engagement to CCR6 were sufficient to induce epithelial cell migration. Consistent with restitution, motogenic concentrations of HBD2 and CCL20 did not induce proliferation. Stimulation with those CCR6 ligands leads to calcium mobilization and elevated active RhoA, phosphorylated myosin light chain, and F-actin accumulation. HBD2 and CCL20 were unable to stimulate migration in the presence of either Rho-kinase or phosphoinositide 3-kinase inhibitors or an intracellular calcium chelator. Together, these data indicate that the canonical wound healing regulatory pathway, along with calcium mobilization, regulates CCR6-directed epithelial cell migration. These findings expand the mechanistic role for chemokines and HBD2 in mucosal inflammation to include immunocyte trafficking and killing of microbes with the concomitant activation of restitutive migration and barrier repair.

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Section: Discussionmentioning

confidence: 99%

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

Vongsa

Zimmerman

Dwinell

2009

Journal of Biological Chemistry

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“…In a study performed in the rat, Chun et al (1997) reported an eightfold increase in intestinal permeability of PEG 4000 three days after exposure to 10 Gy irradiation (Chun et al 1997). Another study carried out in colonic segments of patients subjected to radiation therapy (≥20 Gy) indicated an increase of the passage of mannitol, Dextran 4400, and ovalbumin as compared with nonirradiated patients (Nejdfors et al 2000). However, increased intestinal permeability was also found at irradiation doses that do not induce denudation of intestinal epithelium.…”

Section: Introductionmentioning

confidence: 89%

Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation

Dublineau¹,

Lebrun²,

Grison³

et al. 2004

Can. J. Physiol. Pharmacol.

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Irradiation of the digestive system leads to alterations of the small intestine. We have characterized the disruption of the barrier integrity in rat ileum from 1 to 14 days following irradiation ranging from 6 to 12 Gy. The intestinal permeability to 14C-mannitol and 3H-dextran 70 000 was measured in vitro in Ussing chambers. In parallel to these functional studies, immunohistochemical analyses of junctional proteins (ZO-1 and beta-catenin) of ileal epithelium were performed by confocal microscopy. Irradiation with 10 Gy induced a marked decrease in epithelial tissue resistance at three days and a fivefold increase in mannitol permeability, without modifications of dextran permeability. A disorganization of the localization for ZO-1 and beta-catenin was also observed. At 7 days after irradiation, we observed a recovery of the organization of junctional proteins in parallel to a return of intestinal permeability to control value. In addition to these time-dependent effects, a gradual effect on epithelial integrity of the radiation doses was observed 3 days after irradiation. This study shows a disruption of the integrity of the intestinal barrier in rat ileum following abdominal X-irradiation, depending on the time postirradiation and on the delivered dose. The loss of barrier integrity was characterized by a disorganization of proteins of tight and adherent junctions, leading to increased intestinal permeability to mannitol.

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“…Radiation exposure in cancer patients damages the intestinal epithelium and thus can hamper intestinal barrier function [30].…”

Section: Radiation Injurymentioning

confidence: 99%

Morphology of the Intestinal Barrier in Different Physiological and Pathological Conditions

Khan¹,

Islam²

2012

Histopathology - Reviews and Recent Advances

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Intestinal permeability in humans is increased after radiation therapy

Abstract: Early gastrointestinal complications after radiation therapy may be the result of mucosal atrophy in addition to mucosal damage, with a loss of barrier integrity.

Cited by 82 publications

References 25 publications

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation

Morphology of the Intestinal Barrier in Different Physiological and Pathological Conditions

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