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Oxidized LDL modulates activation of NFκB in mononuclear phagocytes by altering the degradation of IκBs
Author(s) -
Hamilton Thomas A.,
Major Jennifer A.,
Armstrong David,
Tebo Julie M.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.5.667
Subject(s) - nf κb , lipopolysaccharide , transcription factor , iκbα , biology , phagocytosis , nfkb1 , cytokine , gene expression , microbiology and biotechnology , endocrinology , chemistry , signal transduction , immunology , gene , biochemistry
Oxidized low density lipoprotein (oxLDL) is known to alter the expression of inflammatory gene products in mononuclear phagocytes. The mechanisms involved in this effect were studied by examining the activation of nuclear factor κB (NFκB), a transcription factor known to be important in controlling the expression of such genes. Pretreatment of peritoneal macrophages with oxLDL modulated the activation of NFκB in response to either lipopolysaccharide (LPS) or the combination of interferon‐γ (IFN‐γ) and interleukin‐2 (IL‐2). In macrophages pretreated with oxLDL the nuclear translocation of Rel family members (RelA and c‐Rel) is delayed (LPS) or markedly diminished (IFN‐γ/IL‐2) and results in delayed or reduced appearance of κB binding activity within the nucleus. These changes in NFκB activation result from alterations in the stimulus‐dependent degradation of IκBα and IκBβ. The effects of oxLDL on NFκB activation depend both on the degree of LDL oxidation (most potent with extensive oxidation) and on the time of exposure of the cells to the lipoprotein preparation (a minimal exposure of 6 h is required before inhibitory effects are observed). The modulation of IκB/NFκB function in cells exposed to oxLDL appears to be responsible for previously reported effects of oxLDL on chemoattractant cytokine gene expression where both inhibition and delay of such stimulus‐dependent events has been observed. J. Leukoc. Biol. 64: 667–674; 1998.