Possible role of nuclear factor-kappa B activity in germline C epsilon transcription in a human Burkitt lymphoma B cell line.
Nuclear factor-kappa B (NF-kappa B) plays a broad role in gene regulation, but it is not evident whether NF-kappa B acts as a messenger system for germline C epsilon transcription. We report here that the signaling cascade triggered by interleukin-4 (IL-4) or anti-CD40 monoclonal antibody (mAb) participates in NF-kappa B activation responsible for germline C epsilon transcription in a human Burkitt lymphoma B cell line, DND39. Both IL-4 and anti-CD40 mAb induced activation of phosphatidylinositol 3-kinase (PI3-kinase), translocation of a zeta isoform of protein kinase C, and nuclear expression of NF-kappa B. All such events were abrogated by treatment with LY294002, a specific inhibitor of PI3-kinase. In addition, N-acetyl-L-cysteine (NAC), a potent antioxidant, decreased NF-kappa B activation caused by IL-4, anti-CD40 mAb, or their combination. NAC was also effective in diminishing germline C epsilon transcription, and its potency was higher in cultures costimulated with IL-4 and anti-CD40 mAb than in those stimulated with IL-4 alone. These results indicate that IL-4 and ligation of CD40 induce NF-kappa B expression via at least a mechanism dependent on the PI3-kinase pathway and suggest that NF-kappa B sensitive to NAC may play a role in regulating germline C epsilon transcription.
Yanagihara
Y
Y
Clinical Research Center for Allergy, National Sagamihara Hospital, Kanagawa, Japan.
Basaki
Y
Y
Ikizawa
K
K
Kajiwara
K
K
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002051:Burkitt Lymphoma; D019013:CD40 Antigens / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D015847:Interleukin-4 / Q000276:immunology; D007527:Isoenzymes / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D000111:Acetylcysteine; D000975:Antioxidants; D019013:CD40 Antigens; D007127:Immunoglobulin Constant Regions; D015847:Interleukin-4; D007527:Isoenzymes; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C; D000099221:Protein Kinase C zeta