Hydrogen peroxide modulates immunoglobulin expression by targeting the 3'Igh regulatory region through an NFκB-dependent mechanism.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 9423872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1029-2470 (Electronic) Linking ISSN: 10292470 NLM ISO Abbreviation: Free Radic Res Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: Yverdon, Switzerland : New York, NY : Harwood Academic ; distributed by STBS Ltd., c1994-

3' Flanking Region/*drug effects ; Hydrogen Peroxide/*pharmacology ; Immunoglobulin Heavy Chains/*biosynthesis ; Immunoglobulins/*biosynthesis ; NF-kappa B/*metabolism; Animals ; B-Lymphocytes/drug effects ; Cell Line, Tumor ; Electroporation ; I-kappa B Kinase/metabolism ; I-kappa B Proteins ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulins/genetics ; Lipopolysaccharides/pharmacology ; Mice ; NF-KappaB Inhibitor alpha ; Polymerase Chain Reaction ; Promoter Regions, Genetic/drug effects ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects

Reactive oxygen species such as hydrogen peroxide (H(2)O(2)) appear to play a role in signal transduction in immune cells and have been shown to be synthesized upon antigen-mediated activation and to facilitate cellular activation in B- and T-cells. However, an effect of H(2)O(2) on B-cell function (i.e. immunoglobulin (Ig) expression) has been less well-characterized. The effects of H(2)O(2) exposure on lymphocytes may be partly mediated by oxidative modulation of the NFκB signal transduction pathway, which also plays a role in Ig heavy chain (Igh) gene expression. Igh transcription in B lymphocytes is an essential step in antibody production and is governed through a complex interaction of several regulatory elements, including the 3'Igh regulatory region (3'IghRR). Utilizing an in vitro mouse B-cell line model, this study demonstrates that exposure to low μM concentrations of H(2)O(2) can enhance 3'IghRR-regulated transcriptional activity and Igh gene expression, while either higher concentrations of H(2)O(2) or the expression of a degradation resistant inhibitory κB (IκBα super-repressor) can abrogate this effect. Furthermore, suppressive H(2)O(2) concentrations increased protein levels of the p50 NFκB sub-unit, IκBα, and an IκBα immunoreactive band which was previously characterized as an IκBα cleavage product exhibiting stronger inhibitory function than native IκBα. Taken together, these observations suggest that exposure of B lymphocytes to H(2)O(2) can alter Igh transcriptional activity and Ig expression in a complex biphasic manner which appears to be mediated by NFκB and altered 3'IghRR activity. These results may have significant implications to disease states previously associated with the 3'IghRR.
(© 2011 Informa UK, Ltd.)

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R01 ES014676 United States ES NIEHS NIH HHS; R01ES014676 United States ES NIEHS NIH HHS

0 (I-kappa B Proteins)
0 (Immunoglobulin Heavy Chains)
0 (Immunoglobulins)
0 (Lipopolysaccharides)
0 (NF-kappa B)
0 (Nfkbia protein, mouse)
0 (Reactive Oxygen Species)
139874-52-5 (NF-KappaB Inhibitor alpha)
BBX060AN9V (Hydrogen Peroxide)
EC 2.7.11.10 (I-kappa B Kinase)

Date Created: 20110524 Date Completed: 20111206 Latest Revision: 20211020

20231215

PMC4545260

10.3109/10715762.2011.581280

21599461