TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling - PubMed (original) (raw)

TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling

J Mankertz et al. Cell Tissue Res. 2009 Apr.

Abstract

Our aim has been to characterize the molecular mechanisms regulating the expression of the channel-forming tight-junctional protein claudin-2 in response to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha), which is elevated, for example, in active Crohn's disease. TNFalpha caused an 89% decrease of the paracellular resistance in colonic HT-29/B6 cells, whereas transcellular resistance was unaltered. The claudin-2 protein level was increased by TNFalpha without changes in subcellular tight-junctional protein localization as revealed by confocal laser scanning microscopy. Enhanced gene expression was identified as the source of this increase, since claudin-2-specific mRNA and promoter activity was elevated, whereas mRNA stability remained unaltered. Specific inhibitors and phospho-specific antibodies revealed that the increased gene expression of claudin-2 after TNFalpha treatment was mediated by the phosphatidylinositol-3-kinase pathway. Thus, the up-regulation of claudin-2 by TNFalpha is attributable to the regulation of the expression of the gene, as a result of which epithelial barrier function is disturbed, for example, during chronic intestinal inflammation.

PubMed Disclaimer

Similar articles

• Myrrh exerts barrier-stabilising and -protective effects in HT-29/B6 and Caco-2 intestinal epithelial cells.
  Rosenthal R, Luettig J, Hering NA, Krug SM, Albrecht U, Fromm M, Schulzke JD. Rosenthal R, et al. Int J Colorectal Dis. 2017 May;32(5):623-634. doi: 10.1007/s00384-016-2736-x. Epub 2016 Dec 15. Int J Colorectal Dis. 2017. PMID: 27981377
• Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease.
  Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD. Zeissig S, et al. Gut. 2007 Jan;56(1):61-72. doi: 10.1136/gut.2006.094375. Epub 2006 Jul 5. Gut. 2007. PMID: 16822808 Free PMC article.
• TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling.
  Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD. Amasheh M, et al. J Cell Sci. 2010 Dec 1;123(Pt 23):4145-55. doi: 10.1242/jcs.070896. Epub 2010 Nov 9. J Cell Sci. 2010. PMID: 21062898
• The ginger component 6-shogaol prevents TNF-α-induced barrier loss via inhibition of PI3K/Akt and NF-κB signaling.
  Luettig J, Rosenthal R, Lee IM, Krug SM, Schulzke JD. Luettig J, et al. Mol Nutr Food Res. 2016 Dec;60(12):2576-2586. doi: 10.1002/mnfr.201600274. Epub 2016 Sep 16. Mol Nutr Food Res. 2016. PMID: 27487982
• Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells.
  Prasad S, Mingrino R, Kaukinen K, Hayes KL, Powell RM, MacDonald TT, Collins JE. Prasad S, et al. Lab Invest. 2005 Sep;85(9):1139-62. doi: 10.1038/labinvest.3700316. Lab Invest. 2005. PMID: 16007110

Cited by

• Inflammation and the Intestinal Barrier: Leukocyte-Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair.
  Luissint AC, Parkos CA, Nusrat A. Luissint AC, et al. Gastroenterology. 2016 Oct;151(4):616-32. doi: 10.1053/j.gastro.2016.07.008. Epub 2016 Jul 18. Gastroenterology. 2016. PMID: 27436072 Free PMC article. Review.
• TcpC protein from E. coli Nissle improves epithelial barrier function involving PKCζ and ERK1/2 signaling in HT-29/B6 cells.
  Hering NA, Richter JF, Fromm A, Wieser A, Hartmann S, Günzel D, Bücker R, Fromm M, Schulzke JD, Troeger H. Hering NA, et al. Mucosal Immunol. 2014 Mar;7(2):369-78. doi: 10.1038/mi.2013.55. Epub 2013 Jul 31. Mucosal Immunol. 2014. PMID: 23900194
• Bifidobacterium longum supplementation improves age-related delays in fracture repair.
  Roberts JL, Golloshi M, Harding DB, Conduah M, Liu G, Drissi H. Roberts JL, et al. Aging Cell. 2023 Apr;22(4):e13786. doi: 10.1111/acel.13786. Epub 2023 Jan 27. Aging Cell. 2023. PMID: 36704918 Free PMC article.
• The combined effect of food additive titanium dioxide and lipopolysaccharide on mouse intestinal barrier function after chronic exposure of titanium dioxide-contained feedstuffs.
  Zhang Y, Duan S, Liu Y, Wang Y. Zhang Y, et al. Part Fibre Toxicol. 2021 Feb 17;18(1):8. doi: 10.1186/s12989-021-00399-x. Part Fibre Toxicol. 2021. PMID: 33596948 Free PMC article.
• Tight junction CLDN2 gene is a direct target of the vitamin D receptor.
  Zhang YG, Wu S, Lu R, Zhou D, Zhou J, Carmeliet G, Petrof E, Claud EC, Sun J. Zhang YG, et al. Sci Rep. 2015 Jul 27;5:10642. doi: 10.1038/srep10642. Sci Rep. 2015. PMID: 26212084 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Springer