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Stimulation of Epstein‐Barr virus‐infected human B cell growth by physiological concentrations of 4‐hydroxynonenal
Author(s) -
Ranjan Dinesh,
Chen Changguo,
Johnston Thomas D.,
Jeon Hoonbae,
Ibrahim Mohamed,
Drake Jennifer,
Butterfield D. Allan
Publication year - 2006
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1201
Subject(s) - 4 hydroxynonenal , oxidative stress , epstein–barr virus , lipid peroxidation , microbiology and biotechnology , population , b cell , chemistry , cell growth , antibody , western blot , cell , flow cytometry , virus , biology , biochemistry , virology , immunology , medicine , gene , environmental health
We had previously shown that cyclosporin A (CsA) directly promoted the immortalization of Epstein‐Barr virus (EBV)‐infected human B cells (EBV‐B cells) via an oxidative stress mechanism. 4‐Hydroxynonenal (HNE) is a reactive end‐product of lipid peroxidation. We hypothesized that HNE may mediate a direct oxidative stress‐promoting effect of CsA on EBV‐B cells. HNE–protein adducts in CsA‐treated EBV‐B cell extracts were assayed immunochemically using a Slot‐Blot method. Cell proliferation was assayed by [ 3 H]‐thymidine incorporation. EBV oncogene latent membrane protein‐1 (LMP1) expression was assayed by using PE‐conjugated anti‐LMP1 antibody in flow cytometry. We found that CsA at 500 ng ml −1 and 1000 ng ml −1 significantly increased the level of HNE–protein adducts in EBV‐B cells over the control (arbitrary units ± SE) by 251.3 ± 7.5 to 361.3 ± 9.7 and 342.7 ± 10.7, respectively ( p < 0.05, n = 3). EBV‐B cells treated with a physiological concentration of HNE (1 μ M ) for 0.5 and 1 h and cultured for 2 and 4 weeks showed significantly increased [ 3 H]‐thymidine incorporation. EBV‐B cells treated with HNE (1 μ M ) for 1 h and subsequently cultured for 2 and 4 weeks had a significantly higher ( > 2.0 times) LMP1‐positive cell population over the control. In conclusion, in accordance with our previous findings, we show that CsA treatment of EBV‐B cells results in increased production of the lipid peroxidation reactive end‐product HNE that directly promotes EBV‐B cell proliferation and LMP1 expression. This observation provides evidence for further understanding the mechanism of CsA‐induced oxidative stress on EBV‐related post‐transplant lymphoproliferative disorder (PTLD). Copyright © 2005 John Wiley & Sons, Ltd.