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Arsenite stabilizes IκBα and prevents NF‐κB activation in IL‐1 β‐stimulated Caco‐2 cells independent of the heat shock response *
Author(s) -
Hershko Dan D.,
Robb Bruce W.,
Hungness Eric S.,
Luo Guangju,
Hasselgren PerOlof
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10083
Subject(s) - sodium arsenite , arsenite , nf κb , heat shock , iκbα , chemistry , heat shock protein , signal transduction , kinase , biochemistry , microbiology and biotechnology , biology , arsenic , organic chemistry , gene
Recent studies suggest that sodium arsenite downregulates NF‐κB activity by inhibiting phosphorylation and subsequent degradation of IκBα. Many effects of sodium arsenite are secondary to induction of heat shock proteins. The role of the heat shock response in arsenite‐induced inhibition of NF‐κB, however, is not known. We examined the involvement of the heat shock response in arsenite‐induced inhibition of NF‐κB activity in IL‐1β‐stimulated Caco‐2 cells, a human colorectal adenocarcinoma cell line with enterocytic properties. Treatment of the cells with IL‐1β resulted in increased IκB kinase activity, reduced levels of IκBα and increased NF‐κB DNA binding activity. Sodium arsenite blocked all of these responses to IL‐1β without inducing changes in heat shock factor activity or heat shock protein levels. Results from additional experiments showed that the protective effect of sodium arsenite on IκBα was not influenced by the oxygen radical scavenger catalase or by inhibitors of the MAP‐kinase signaling pathway. The present results suggest that sodium arsenite stabilizes IκBα and prevents NF‐κB activation in IL‐1β‐stimulated Caco‐2 cells independent of the heat shock response. In addition, stabilization of IκBα by sodium arsenite does not require oxygen radical formation or activation of the MAP kinase signaling pathway. J. Cell. Biochem. 84: 687–698, 2002. © 2002 Wiley‐Liss, Inc.