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IL-1beta causes an increase in intestinal epithelial tight junction permeability.
J Immunol. 2007 Apr 01; 178(7):4641-9.JI

Abstract

IL-1beta is a prototypical proinflammatory cytokine that plays a central role in the intestinal inflammation amplification cascade. Recent studies have indicated that a TNF-alpha- and IFN-gamma-induced increase in intestinal epithelial paracellular permeability may be an important mechanism contributing to intestinal inflammation. Despite its central role in promoting intestinal inflammation, the role of IL-1beta on intestinal epithelial tight junction (TJ) barrier function remains unclear. The major aims of this study were to determine the effect of IL-1beta on intestinal epithelial TJ permeability and to elucidate the mechanisms involved in this process, using a well-established in vitro intestinal epithelial model system consisting of filter-grown Caco-2 intestinal epithelial monolayers. IL-1beta (0-100 ng/ml) produced a concentration- and time-dependent decrease in Caco-2 transepithelial resistance. Conversely, IL-1beta caused a progressive time-dependent increase in transepithelial permeability to paracellular marker inulin. IL-1beta-induced increase in Caco-2 TJ permeability was accompanied by a rapid activation of NF-kappaB. NF-kappaB inhibitors, pyrrolidine dithiocarbamate and curcumin, prevented the IL-1beta-induced increase in Caco-2 TJ permeability. To further confirm the role of NF-kappaB in the IL-1beta-induced increase in Caco-2 TJ permeability, NF-kappaB p65 expression was silenced by small interfering RNA transfection. NF-kappaB p65 depletion completely inhibited the IL-1beta-induced increase in Caco-2 TJ permeability. IL-1beta did not induce apoptosis in the Caco-2 cell. In conclusion, our findings show for the first time that IL-1beta at physiologically relevant concentrations causes an increase in intestinal epithelial TJ permeability. The IL-1beta-induced increase in Caco-2 TJ permeability was mediated in part by the activation of NF-kappaB pathways but not apoptosis.

Authors+Show Affiliations

Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17372023

Citation

Al-Sadi, Rana M., and Thomas Y. Ma. "IL-1beta Causes an Increase in Intestinal Epithelial Tight Junction Permeability." Journal of Immunology (Baltimore, Md. : 1950), vol. 178, no. 7, 2007, pp. 4641-9.
Al-Sadi RM, Ma TY. IL-1beta causes an increase in intestinal epithelial tight junction permeability. J Immunol. 2007;178(7):4641-9.
Al-Sadi, R. M., & Ma, T. Y. (2007). IL-1beta causes an increase in intestinal epithelial tight junction permeability. Journal of Immunology (Baltimore, Md. : 1950), 178(7), 4641-9.
Al-Sadi RM, Ma TY. IL-1beta Causes an Increase in Intestinal Epithelial Tight Junction Permeability. J Immunol. 2007 Apr 1;178(7):4641-9. PubMed PMID: 17372023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1beta causes an increase in intestinal epithelial tight junction permeability. AU - Al-Sadi,Rana M, AU - Ma,Thomas Y, PY - 2007/3/21/pubmed PY - 2007/6/20/medline PY - 2007/3/21/entrez SP - 4641 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 178 IS - 7 N2 - IL-1beta is a prototypical proinflammatory cytokine that plays a central role in the intestinal inflammation amplification cascade. Recent studies have indicated that a TNF-alpha- and IFN-gamma-induced increase in intestinal epithelial paracellular permeability may be an important mechanism contributing to intestinal inflammation. Despite its central role in promoting intestinal inflammation, the role of IL-1beta on intestinal epithelial tight junction (TJ) barrier function remains unclear. The major aims of this study were to determine the effect of IL-1beta on intestinal epithelial TJ permeability and to elucidate the mechanisms involved in this process, using a well-established in vitro intestinal epithelial model system consisting of filter-grown Caco-2 intestinal epithelial monolayers. IL-1beta (0-100 ng/ml) produced a concentration- and time-dependent decrease in Caco-2 transepithelial resistance. Conversely, IL-1beta caused a progressive time-dependent increase in transepithelial permeability to paracellular marker inulin. IL-1beta-induced increase in Caco-2 TJ permeability was accompanied by a rapid activation of NF-kappaB. NF-kappaB inhibitors, pyrrolidine dithiocarbamate and curcumin, prevented the IL-1beta-induced increase in Caco-2 TJ permeability. To further confirm the role of NF-kappaB in the IL-1beta-induced increase in Caco-2 TJ permeability, NF-kappaB p65 expression was silenced by small interfering RNA transfection. NF-kappaB p65 depletion completely inhibited the IL-1beta-induced increase in Caco-2 TJ permeability. IL-1beta did not induce apoptosis in the Caco-2 cell. In conclusion, our findings show for the first time that IL-1beta at physiologically relevant concentrations causes an increase in intestinal epithelial TJ permeability. The IL-1beta-induced increase in Caco-2 TJ permeability was mediated in part by the activation of NF-kappaB pathways but not apoptosis. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/17372023/IL_1beta_causes_an_increase_in_intestinal_epithelial_tight_junction_permeability_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=17372023 DB - PRIME DP - Unbound Medicine ER -