The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Interferon-γ decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin
Abstract
The effects of interferon-γ (IFN-γ) on tight junctions in T84 human intestinal epithelial cells were investigated. Treatment of T84 cells with IFN-γ caused a dose- and time-dependent increase in monolayer permeability as assessed by transepithelial electrical resistance measurements. Examination of specific proteins associated with tight junctions by immunoblotting and confocal microscopy revealed changes in the expression levels and localization of some of these proteins after exposure of the cells to IFN-γ. Specifically, IFN-γ treatment resulted in an almost total loss of zonula occludens (ZO)-1, whereas the levels of ZO-2 and occludin showed relatively modest decreases compared with untreated cells. Loss of ZO-1 was associated with the altered localization of ZO-2 and occludin. In IFN-γ-treated cells, ZO-2 and occludin were diffusely distributed, whereas, in control cells, they, along with ZO-1, were predominantly localized to the tight junctions. Analysis of ZO-1 protein and RNA by pulse chase and RT-PCR, respectively, showed an increase in protein turnover, a decrease in protein synthesis, and a reduction in RNA levels following IFN-γ treatment. In contrast to ZO-1, ZO-2 and occludin did not show any major changes in these parameters. In addition, the organization of actin in the apical and tight junction regions, but not in the mid- or basal regions, of the cells was also perturbed by IFN-γ treatment of cells. Time-course analysis of IFN-γ-induced alterations in ZO-1 expression and apical actin perturbation indicated that these two effects were intimately linked and could not be dissociated. These results suggest that IFN-γ affects barrier function in T84 cells by decreasing the levels of ZO-1 and perturbing apical actin organization, which leads to a disorganization of the tight junction and an increase in paracellular permeability.
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Cites
Occludin: a novel integral membrane protein localizing at tight junctions.
Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., Tsukita, S., & Tsukita, S. (1993) · The Journal of cell biology · doi:10.1083/jcb.123.6.1777 · Cited by 2,580
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Martìn-Padura, I., Lostaglio, S., Schneemann, M., Williams, L., Romano, M., Fruscella, P., Panzeri, C., Stoppacciaro, A., Ruco, L., Villa, A., et al. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.1.117 · Cited by 1,388
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Tight junctions and the molecular basis for regulation of paracellular permeability
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Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers.
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Cited by
Tight Junctions and Cell Polarity
Shin, K., Fogg, V. C., & Margolis, B. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104219 · Cited by 745
Cytokine regulation of tight junctions
Capaldo, C. T., & Nusrat, A. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.08.027 · Cited by 718
Wang, F., Graham, W. V., Wang, Y., Witkowski, E. D., Schwarz, B. T., & Turner, J. R. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62264-x · Cited by 696
Lam, Y. Y., Ha, C. W. Y., Campbell, C. R., Mitchell, A. J., Dinudom, A., Oscarsson, J., Cook, D. I., Hunt, N. H., Caterson, I. D., Holmes, A. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034233 · Cited by 604
Luissint, A.-C., Parkos, C. A., & Nusrat, A. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.07.008 · Cited by 555
Metadata
- Authors
- Youakim, A., & Ahdieh, M.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 1999-05-01
- Volume
- 276
- Issue
- 5
- Pages
- G1279-G1288
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2121527471
- Cited by
- 286
- References
- 35
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
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- Youakim, A., & Ahdieh, M. (1999). Interferon-γ decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin. American Journal of Physiology-Gastrointestinal and Liver Physiology. https://doi.org/10.1152/ajpgi.1999.276.5.g1279
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