Okadaic acid is a potent inducer of AP-1, NF-kappa B, and tumor necrosis factor-alpha in human B lymphocytes.
Treatment of human B lymphocytes with an optimal concentration of okadaic acid, an inhibitor of phosphatases 1 and 2A, resulted in the induction of the transcription factor, AP-1 and a marked increase in NF-kappa B levels. In contrast, no effect on the levels of the octamer binding proteins, Oct-1 or Oct-2, were found. Since both AP-1 and NF-kappa B have been reported to be important in the induction of the tumor necrosis factor-alpha (TNF-alpha) gene we examined the effects of okadaic acid on TNF-alpha mRNA levels. Treatment with okadaic acid resulted in a striking increase in TNF-alpha mRNA transcripts within 1 h of stimulation and large amounts of TNF-alpha were released into the culture media. Although okadaic acid provides a potent inductive signal for AP-1 and NF-kappa B it did not induce either B cell proliferation or immunoglobulin secretion.
Rieckmann
P
P
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Thévenin
C
C
Kehrl
J H
JH
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis*; D019319:Okadaic Acid; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D004988:Ethers, Cyclic; D007136:Immunoglobulins; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019319:Okadaic Acid; D003513:Cycloheximide