gut: IFN-gamma modulation of epithelial barrier function

[Guest guest]

Jyonouchi has been known to cite RB et al. Additional cites herein

are consistent with Jyonouchi's calling attention to irregularities of

innate immunity in regard to autistic children's peripheral cytokines

and responses to dietary protein antigens. The gist of these citations

is that certain cytokines increase intestinal permeability.

//

IFN-gamma modulation of epithelial barrier function. Time course,

reversibility, and site of cytokine binding.

<http://www.ncbi.nlm.nih.gov/pubmed/8450217>

RB, Planchon SM, Roche JK.

J Immunol. 1993 Mar 15;150(6):2356-63.

The single cell-thick intestinal epithelium forms a crucial barrier

between the host and environment, and is modeled in vitro by a monolayer

of polarized, highly differentiated T84 epithelial cells impermeable to

most macromolecules because of functional intercellular tight junctions.

Absence of a permeability defect across the monolayer, either

transcellular or paracellular, is indicated by development of a

transepithelial electrical resistance of > or = 1000 ohm-cm2, reported

to be markedly diminished by exposure to a T lymphocyte cytokine,

IFN-gamma. We sought to define this phenomenon in four ways by

determining its duration and reversibility; the uniqueness of type II

(gamma) IFN as opposed to type I (alpha) IFN; the surface of the

polarized columnar epithelium likely involved in responding to

IFN-gamma; and whether a specific surface membrane receptor on the

epithelial cell participates in the response. Using a special apparatus

that allows differential cytokine exposure of monolayer surfaces, our

data demonstrate 1) only the monolayer's basolateral surface is

IFN-gamma responsive, whereas the apical (microvillous) surface is no;

2) the alteration in electrical resistance of epithelium is prolonged (5

days), even after a single (24 h) exposure to IFN-gamma, but

nevertheless is reversible; 3) the effect is likely receptor-ligand

mediated, because it can be partially blocked by IFN-gamma

receptor-specific monoclonal Ig; 4) an alteration in tight junction

function (a paracellular pathway) rather than cell necrosis or a

transcellular pathway is responsible for IFN-gamma-induced monolayer

dysfunction because permeability to a 44,000-Da macromolecule

(horseradish peroxidase) did not increase, and intracytoplasmic T84 cell

enzymes were not released into the media; and 5) the biologic phenomenon

could not be induced by a species (alpha) of class I IFN, making

IFN-gamma reasonably unique in this regard. Given the proximity;

activation status, and capacity of T lymphocytes for cytokine production

in mucosa, we suggest that IFN-gamma-induced changes in epithelial

permeability may be a major cause of altered intestinal barrier function

in vivo.

open access:

Mechanism of interferon-gamma-induced increase in T84 intestinal

epithelial tight junction. <http://www.ncbi.nlm.nih.gov/pubmed/19128033>

Boivin MA, Roy PK, Bradley A, Kennedy JC, Rihani T, Ma TY.

J Interferon Cytokine Res. 2009 Jan;29(1):45-54.

Epithelial NF-kappaB enhances transmucosal fluid movement by altering

tight junction protein composition after T cell activation.

<http://www.ncbi.nlm.nih.gov/pubmed/20008138>

Tang Y, Clayburgh DR, Mittal N, Goretsky T, et al.

Am J Pathol. 2010 Jan;176(1):158-67.

IL-1beta causes an increase in intestinal epithelial tight junction

permeability. <http://www.ncbi.nlm.nih.gov/pubmed/17372023>

Al-Sadi RM, Ma TY.

J Immunol. 2007 Apr 1;178(7):4641-9.

Molecular mechanism of tumor necrosis factor-alpha modulation of

intestinal epithelial tight junction barrier.

<http://www.ncbi.nlm.nih.gov/pubmed/16474009>

Ye D, Ma I, Ma TY.

Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G496-504.

Even low-grade inflammation impacts on small intestinal function.

<http://www.ncbi.nlm.nih.gov/pubmed/20205274>

Peuhkuri K, Vapaatalo H, Korpela R.

World J Gastroenterol. 2010 Mar 7;16(9):1057-62.

Cytokine regulation of tight junctions.

<http://www.ncbi.nlm.nih.gov/pubmed/18952050>

Capaldo CT, Nusrat A.

Biochim Biophys Acta. 2009 Apr;1788(4):864-71.

Effect of natural commensal-origin DNA on toll-like receptor 9 (TLR9)

signaling cascade, chemokine IL-8 expression, and barrier integritiy of

polarized intestinal epithelial cells.

<http://www.ncbi.nlm.nih.gov/pubmed/19714766>

Ghadimi D, Vrese M, Heller KJ, Schrezenmeir J.

Inflamm Bowel Dis. 2010 Mar;16(3):410-27.

Immunomodulatory mechanisms of lactobacilli.

<http://www.ncbi.nlm.nih.gov/pubmed/21995674>

Wells JM.

Microb Cell Fact. 2011 Aug 30;10 Suppl 1:S17

Probiotics, nuclear receptor signaling, and anti-inflammatory pathways.

<http://www.ncbi.nlm.nih.gov/pubmed/21808643>

Yoon SS, Sun J.

Gastroenterol Res Pract. 2011;2011:971938.

TNF-alpha-induced increase in intestinal epithelial tight junction

permeability requires NF-kappa B activation.

<http://www.ncbi.nlm.nih.gov/pubmed/14766535>

Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HM.

Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G367-76.

" Inhibition of TNF-alpha-induced NF-kappa B activation by selected

NF-kappa B inhibitors, */curcumin/* and triptolide, prevented the

increase in Caco-2 TJ permeability, indicating that NF-kappa B

activation was required for the TNF-alpha-induced increase in Caco-2 TJ

permeability. "

PS: This post may be forwarded hither & yon.