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TNFα-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFκB signaling

Amasheh, Maren, Fromm, Anja, Krug, Susanne M., Amasheh, Salah, Andres, Susanne, Zeitz, Martin, Fromm, Michael, Schulzke, Jörg-Dieter·2010·Journal of Cell Science

Abstract

TNFα-mediated tight junction defects contribute to diarrhea in inflammatory bowel diseases (IBDs). In our study, the signaling pathways of the TNFα effect on barrier- or pore-forming claudins were analyzed in HT-29/B6 human colon monolayers. Berberine, a herbal therapeutic agent that has been recently established as a therapy for diabetes and hypercholesterinemia, was able to completely antagonize the TNFα-mediated barrier defects in the cell model and in rat colon. Ussing chamber experiments and two-path impedance spectroscopy revealed a decrease of paracellular resistance after TNFα to 11±4%, whereas transcellular resistance was unchanged. The permeability of the paracellular marker fluorescein was increased fourfold. Berberine alone had no effect while it fully prevented the TNFα-induced barrier defects. This effect on resistance was confirmed in rat colon. TNFα removed claudin-1 from the tight junction and increased claudin-2 expression. Berberine prevented TNFα-induced claudin-1 disassembly and upregulation of claudin-2. The effects of berberine were mimicked by genistein plus BAY11-7082, indicating that they are mediated via tyrosine kinase, pAkt and NFκB pathways. In conclusion, the anti-diarrheal effect of berberine is explained by a novel mechanism, suggesting a therapeutic approach against barrier breakdown in intestinal inflammation.

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Metadata

Authors
Amasheh, M., Fromm, A., Krug, S. M., Amasheh, S., Andres, S., Zeitz, M., Fromm, M., & Schulzke, J.-D.
Venue
Journal of Cell Science
Published
2010-12-01
Volume
123
Issue
23
Pages
4145-4155
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W1966185510
Cited by
224
References
5
FWCI
7.82
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: TNFα-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFκB signaling. https://app.cochat.ai/papers/10.1242/jcs.070896
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Amasheh, M., Fromm, A., Krug, S. M., Amasheh, S., Andres, S., Zeitz, M., Fromm, M., & Schulzke, J.-D. (2010). TNFα-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFκB signaling. Journal of Cell Science. https://doi.org/10.1242/jcs.070896

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