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TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation.
Am J Physiol Gastrointest Liver Physiol. 2004 Mar; 286(3):G367-76.AJ

Abstract

Crohn's disease (CD) patients have an abnormal increase in intestinal epithelial permeability. The defect in intestinal tight junction (TJ) barrier has been proposed as an important etiologic factor of CD. TNF-alpha increases intestinal TJ permeability. Because TNF-alpha levels are markedly increased in CD, TNF-alpha increase in intestinal TJ permeability could be a contributing factor of intestinal permeability defect in CD. Our purpose was to determine some of the intracellular mechanisms involved in TNF-alpha modulation of intestinal epithelial TJ permeability by using an in vitro intestinal epithelial system consisting of filter-grown Caco-2 monolayers. TNF-alpha produced a concentration- and time-dependent increase in Caco-2 TJ permeability. TNF-alpha-induced increase in Caco-2 TJ permeability correlated with Caco-2 NF-kappa B activation. 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. This increase in Caco-2 TJ permeability was accompanied by down-regulation of zonula occludens (ZO)-1 proteins and alteration in junctional localization of ZO-1 proteins. TNF-alpha modulation of ZO-1 protein expression and junctional localization were also prevented by NF-kappa B inhibitors. TNF-alpha did not induce apoptosis in Caco-2 cells, suggesting that apoptosis was not the mechanism involved in TNF-alpha-induced increase in Caco-2 TJ permeability. These results demonstrate for the first time that TNF-alpha-induced increase in Caco-2 TJ permeability was mediated by NF-kappa B activation. The increase in permeability was associated with NF-kappa B-dependent downregulation of ZO-1 protein expression and alteration in junctional localization.

Authors+Show Affiliations

Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131-0001, USA. tma@salud.unm.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14766535

Citation

Ma, Thomas Y., et al. "TNF-alpha-induced Increase in Intestinal Epithelial Tight Junction Permeability Requires NF-kappa B Activation." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 286, no. 3, 2004, pp. G367-76.
Ma TY, Iwamoto GK, Hoa NT, et al. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol. 2004;286(3):G367-76.
Ma, T. Y., Iwamoto, G. K., Hoa, N. T., Akotia, V., Pedram, A., Boivin, M. A., & Said, H. M. (2004). TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. American Journal of Physiology. Gastrointestinal and Liver Physiology, 286(3), G367-76.
Ma TY, et al. TNF-alpha-induced Increase in Intestinal Epithelial Tight Junction Permeability Requires NF-kappa B Activation. Am J Physiol Gastrointest Liver Physiol. 2004;286(3):G367-76. PubMed PMID: 14766535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. AU - Ma,Thomas Y, AU - Iwamoto,Gary K, AU - Hoa,Neil T, AU - Akotia,Vimesh, AU - Pedram,Ali, AU - Boivin,Michel A, AU - Said,Hamid M, PY - 2004/2/10/pubmed PY - 2004/3/18/medline PY - 2004/2/10/entrez SP - G367 EP - 76 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 286 IS - 3 N2 - Crohn's disease (CD) patients have an abnormal increase in intestinal epithelial permeability. The defect in intestinal tight junction (TJ) barrier has been proposed as an important etiologic factor of CD. TNF-alpha increases intestinal TJ permeability. Because TNF-alpha levels are markedly increased in CD, TNF-alpha increase in intestinal TJ permeability could be a contributing factor of intestinal permeability defect in CD. Our purpose was to determine some of the intracellular mechanisms involved in TNF-alpha modulation of intestinal epithelial TJ permeability by using an in vitro intestinal epithelial system consisting of filter-grown Caco-2 monolayers. TNF-alpha produced a concentration- and time-dependent increase in Caco-2 TJ permeability. TNF-alpha-induced increase in Caco-2 TJ permeability correlated with Caco-2 NF-kappa B activation. 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. This increase in Caco-2 TJ permeability was accompanied by down-regulation of zonula occludens (ZO)-1 proteins and alteration in junctional localization of ZO-1 proteins. TNF-alpha modulation of ZO-1 protein expression and junctional localization were also prevented by NF-kappa B inhibitors. TNF-alpha did not induce apoptosis in Caco-2 cells, suggesting that apoptosis was not the mechanism involved in TNF-alpha-induced increase in Caco-2 TJ permeability. These results demonstrate for the first time that TNF-alpha-induced increase in Caco-2 TJ permeability was mediated by NF-kappa B activation. The increase in permeability was associated with NF-kappa B-dependent downregulation of ZO-1 protein expression and alteration in junctional localization. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/14766535/TNF_alpha_induced_increase_in_intestinal_epithelial_tight_junction_permeability_requires_NF_kappa_B_activation_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00173.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -