Disruption of the actin cytoskeleton results in nuclear factor-κB activation and inflammatory mediator production in cultured human intestinal epithelial cells

Zoltán H. Németh, Edwin A. Deitch, Marson T. Davidson, Csaba Szabo, E. Sylvester Vizi, György Haskó

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The cytoskeleton in eukaryotic cells is composed of two major filament systems, the microtubule system and the actin cytoskeleton. The microtubule system has recently emerged as an important regulator of NF-κB function. However, the role that the actin microfilament system plays in controlling NF-κB activation is incompletely understood. In this study, we examined the effect of actin cytoskeleton disruption on NF-κB activation in human intestinal epithelial cells. Treatment of HT-29 or Caco-2 cells with the prototypic actin disrupting agents cytochalasin D or latrunculin B resulted in increased NF-κB DNA binding and NF-κB-dependent transcriptional activity. This NF-κB activation by cytochalasin D was secondary to an effect on IκB, because cytochalasin D-induced IκB degradation and the cytochalasin D-induced increase in NF-κB-dependent transcriptional activity was prevented by a dominant negative IκB mutant. Exposure of the cells to cytochalasins or latrunculin B increased gene expression and release of the NF-κB-dependent chemokines IL-8 and GRO-α. Cytochalasin D also activated p38 MAP kinase, which pathway contributed to the cytochalasin D-induced increase in IL-8 production. These results demonstrate that the actin cytoskeleton plays an important role in the regulation of NF-κB activation and inflammatory events in intestinal epithelial cells.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalJournal of Cellular Physiology
Volume200
Issue number1
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Cytochalasin D
Actin Cytoskeleton
Actins
Epithelial Cells
Chemical activation
Cytochalasin B
Interleukin-8
Microtubules
Caco-2 Cells
Eukaryotic Cells
p38 Mitogen-Activated Protein Kinases
Cytoskeleton
Chemokines
Gene expression
Gene Expression
Degradation
DNA

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Disruption of the actin cytoskeleton results in nuclear factor-κB activation and inflammatory mediator production in cultured human intestinal epithelial cells. / Németh, Zoltán H.; Deitch, Edwin A.; Davidson, Marson T.; Szabo, Csaba; Vizi, E. Sylvester; Haskó, György.

In: Journal of Cellular Physiology, Vol. 200, No. 1, 07.2004, p. 71-81.

Research output: Contribution to journalArticle

Németh, Zoltán H. ; Deitch, Edwin A. ; Davidson, Marson T. ; Szabo, Csaba ; Vizi, E. Sylvester ; Haskó, György. / Disruption of the actin cytoskeleton results in nuclear factor-κB activation and inflammatory mediator production in cultured human intestinal epithelial cells. In: Journal of Cellular Physiology. 2004 ; Vol. 200, No. 1. pp. 71-81.
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