Cytokine regulation by platelet-activating factor in a human B cell line.
TNF-alpha is an inflammatory cytokine produced by B cells that also impacts B cell differentiation and Ig secretion. We have investigated the regulation of the TNF-alpha gene in a human B cell line in response to platelet-activating factor (PAF), a potent phospholipid often produced in inflammatory reactions. We report here that PAF increases the RNA levels for the TNF-alpha gene in the human B cell line Ramos. This is mediated by an increase in the transcription rate and a longer half-life of the TNF-alpha transcripts. Induction of the TNF-alpha gene is rapid in these cells and independent of new protein synthesis. Despite increasing RNA for the TNF-alpha gene, PAF increases TNF-alpha protein levels only in the presence of a costimulus, such as PMA. We hypothesize that PAF acts at the transcriptional level to increase TNF-alpha RNA, but a post-transcriptional block acts to regulate protein production. We also report that PAF enhances PMA-induced TNF-alpha production from human peripheral B cells. This increase is maximal at 0.1 microM PAF and is blocked by PAF receptor antagonists. The ability of PAF to modulate cytokine production from human B cells provides further evidence that PAF has a role in B cell biology and suggests it may be important in conditions involving B cell-derived cytokines.
Smith
C S
CS
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Parker
L
L
Shearer
W T
WT
D001402:B-Lymphocytes / Q000276:immunology*; D015152:Blotting, Northern; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010972:Platelet Activating Factor / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate