Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers.

Madara, J L; Stafford, J

doi:10.1172/jci113938

Cited by 722 publications

(455 citation statements)

References 21 publications

(19 reference statements)

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“…However, we have previously shown that prolonged exposure of monolayers to IFN-3, also decreases baseline monolayer resistance (Madara and Stafford, 1989) and the same effect was noted here (344 + 70, 461 + 20, and 721 + 27 ohm-cm 2 for exposure times of 72, 48, and 0 h, respectively, to 1,000 U/ml IFN-7). However, the effects of IFN-3, on PMN transepithelial migration were not explained by a secondary effect of IFN-'y permeability since the effects on transmigration predated IFN--r resistance alterations.…”

Section: Ifn-y Modulates Pmn Migration In Thesupporting

confidence: 89%

“…As shown in Fig. 2 B, and as we have previously described (Madara and Stafford, 1989), baseline resistance is unaffected by monolayer exposure to 1,000 U/ml IFN-'y for 24 h (721 + 27 vs. 715 + 42 ohm.cm 2 for control and 24-h IFN--r exposure, respectively, p > 0.05). In contrast (Fig.…”

Section: Ifn-y Modulates Pmn Migration In Thesupporting

confidence: 83%

“…cm 2 vs. 1,184 + 81 ohm.cm 2 for cycloheximide-treated control monolayers, p > 0.05). We also noted that, interestingly, the drop in transepithelial resistance after prolonged exposure to IFN-3, (1,000 U/ml, 72 h) which we have previously described (Madara and Stafford, 1989), is largely cy- Figure 10. Epithelial preexposure to IFN-3, increases monolayer-associated PMN after basolateral-to-apical directed transmigration.…”

Section: Effect Of Cycloheximide On the Modulation Of Pmn Transepithesupporting

confidence: 57%

“…Thus, IFN--~ is likely an important cytokine in the intestinal epithelial microenvironment. Epithelia, including our model intestinal epithelial cell line (Madara and Stafford, 1989), appear to express receptors for IFN-% Lastly, IFN-3, appears capable of modulating the intestinal epithelial cell surface with which a transmigrating neutrophil must interface. For example, IFN-v exposure elicits MHC class II antigen expression on intestinal epithelia (Mayer et al, 1991).…”

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confidence: 97%

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Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion.

Colgan

Parkos

Delp

et al. 1993

The Journal of Cell Biology

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Abstract. Neutrophil, or polymorphonuclear leukocyte (PMN), migration across intestinal epithelial barriers, such as occurs in many disease states, appears to result in modifications of epithelial barrier and ion transport functions (Nash, S., J. Stafford, and J. L. . Z Clin. Invest. 80:1104-1113; Madara, J. L., C. A. Parkos, S. P. Colgan, R. J. MacLeod, S. Nash, J. B. Matthews, C. Delp, and W. I. Lencer. 1992. J. Clin. Invest. 89:1938-1944). Here we investigate the effects of epithelial exposure to IFN-,), on PMN migration across cultured monolayers of the human intestinal epithelial cell line Tu. Transepithelial migration of PMN was initially assessed in the apicalto-basolateral direction, since previous studies indicate general qualitative similarities between PMN migration in the apical-to-basolateral and in the basolateralto-apical directions. In the apical-to-basolateral direction, epithelial exposure to IFN-.,/rnarkedly upregulated transepithelial migration of PMN in a dose-and timedependent fashion as measured by both electrical and myeloperoxidase assays. This IFN-~/-elicited effect on transmigration was specifically due to a IFN-,/effect on epithelial cells and was not secondary to IFN-,y effects on epithelial tight junction permeability. Moreover, this IFN-.y effect was dependent on epithelial protein synthesis, and involved a pathway in which CDllb/18, but not ICAM-1 or CDlla/18, appeared to play a crucial role in PMN-epithelial adhesion. IFN-~/also substantially modified PMN transepithelial migration in the natural, basolateral-to-apical direction. The IFN-'y effect on naturally directed transmigration was also specifically due to an IFN-3, effect on epithelial cells, showed comparable time and dose dependency to that of oppositely directed migration, was CDllb/18 dependent, and required epithelial protein synthesis. Additionally, however, important qualitative differences existed in how IFN-3, affected transmigration in the two directions. In contrast to apical-to-basolateral directed migration, IFN-,), markedly downregulated transepithelial migration of PMN in the natural direction. This downregulation of PMN migration in the natural direction, however, was not due to failure of PMN to move across filters and into monolayers. Indeed, IFN-3, exposure to epithelia increased the number of PMN which had moved into the basolateral space of the epithelium in naturally directed transmigration. These results represent the first detailed report of influences on PMN transepithelial migration by a cytokine, define conditions under which a qualitative difference in PMN transepithelial migration exists, and suggest that migration of PMN across epithelia in the natural direction may involve multiple steps which can be differentially regulated by cytokines. Specifically, it appears that in naturally directed migration, IFN-~/ may enhance the retention time of the recruited PMN in the paracellular space below tight junctions, and does so, at least in part, by downregulating a PMN-epithelial interactive event req...

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Section: Ifn-y Modulates Pmn Migration In Thesupporting

confidence: 89%

Section: Ifn-y Modulates Pmn Migration In Thesupporting

confidence: 83%

Section: Effect Of Cycloheximide On the Modulation Of Pmn Transepithesupporting

confidence: 57%

mentioning

confidence: 97%

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Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion.

Colgan

Parkos

Delp

et al. 1993

The Journal of Cell Biology

Self Cite

158

111

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“…IFN-␥ and TNF-␣ cause a functional disruption of epithelial tight junctions. 22,23 To determine if, in addition to preventing the increased mucosal secretion of proinflammatory cytokines, probiotics were effective in maintaining gut barrier function, the colonic permeability was assessed by the measurement of the mannitol flux in Ussing chambers. Preliminary experiments confirmed that following the injection of LPS/GalN, mice demonstrated a maximal enhanced colonic mannitol flux 6 hours following injection (data not shown); thus, all subsequent measurements were made at this time.…”

Section: Resultsmentioning

confidence: 99%

Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis

et al. 2007

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A breakdown in intestinal barrier function and increased bacterial translocation are key events in the pathogenesis of sepsis and liver disease. Altering gut microflora with noninvasive and immunomodulatory probiotic organisms has been proposed as an adjunctive therapy to reduce the level of bacterial translocation and prevent the onset of sepsis. The purpose of this study was to determine the efficacy of a probiotic compound in attenuating hepatic and intestinal injury in a mouse model of sepsis. Wild-type and interleukin-10 (IL-10) gene-deficient 129 Sv/Ev mice were fed the probiotic compound VSL#3 for 7 days. To induce sepsis, the mice were injected with lipopolysaccharide (LPS) and D-galactosamine (GalN) in the presence and absence of the peroxisome proliferator-activated receptor gamma (PPAR␥) inhibitor GW9662. The mice were killed after 6 hours, and their colons were removed for the measurement of the cytokine production and epithelial function. The functional permeability was assessed by the mannitol movement and cyclic adenosine monophosphate-dependent chloride secretion in tissue mounted in Ussing chambers. The livers were analyzed for bacterial translocation, cytokine production, histological injury, and PPAR␥ levels. The tissue levels of tumor necrosis factor alpha, interferon gamma, IL-6, and IL-12p35 ribonucleic acid were measured by semiquantitative reverse transcription polymerase chain reaction. L iver dysfunction and failure contribute to the high mortality rates seen in patients with Gram-negative sepsis. The presence of lipopolysaccharide (LPS) from Gram-negative bacteria in the systemic circulation results in the activation of the innate immune system and the secretion of high levels of proinflammatory cytokines. In animal models, LPS challenge can induce a systemic reaction resulting in a sepsis-like condition characterized by fever, hypotension, and widespread tissue damage. D-Galactosamine (GalN) increases the susceptibility of mice to LPS-induced shock by impairing liver metabolism. 1 Challenging mice with low doses of LPS in conjunction with GalN results in massive liver apoptosis and increased mortality.Tumor necrosis factor alpha (TNF-␣) plays a central role in the overwhelming systemic inflammatory response to LPS. 2 However, the complete blockade of TNF-␣ production does not improve survival in animals or humans 3 The activation of nuclear factor kappa B (NF-B) has been shown to play a key role in the pathogenesis of sepsis and is a pivotal step in the regulation of several immune and proinflammatory genes, including TNF-␣. 4 The modulation of NF-B activity has been proposed as a strategy for reducing the mortality associated with sepsis. Peroxisome proliferator-activated receptor gamma (PPAR␥) is a nuclear hormone receptor and transcription

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Apoptosis of Crypt Epithelial Cells in Ulcerative Colitis

et al. 1996

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In the colon of ulcerative colitis (UC) patients, apoptotic bodies have been recognized in routine histopathological preparations. To investigate the extent of the apoptosis, colonic biopsies were examined from involved and uninvolved areas of untreated active UC and from normal areas in patients with colonic polyps, utilizing various markers of apoptosis. The markers included DNA breaks detected by TUNEL, Fas (CD95/APO‐1) and Fas ligand (Fas‐L) localized by immunohistochemistry, electron microscopic features of apoptosis, and laddering of extracted DNA. Apoptosis marker positive cells were found mainly on the luminal epithelium of the normal colon and were present in active UC in crypts of involved and uninvolved areas of the colon, in addition to the luminal epithelium. The DNA extracted from active UC colon electrophoresed as a ladder. These findings suggest that the loss of epithelial cells in active UC occurs mainly by apoptosis in crypts of involved and adjacent uninvolved areas and that the Fas/Fas‐L interaction is a mediator of the apoptosis.

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Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers.

Cited by 722 publications

References 21 publications

Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion.

Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion.

Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis

Apoptosis of Crypt Epithelial Cells in Ulcerative Colitis

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