Smith C S, Parker L, Shearer W T
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
J Immunol. 1994 Nov 1;153(9):3997-4005.
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.
肿瘤坏死因子-α（TNF-α）是一种由B细胞产生的炎性细胞因子，它也会影响B细胞分化和免疫球蛋白（Ig）分泌。我们研究了人类B细胞系中TNF-α基因对血小板活化因子（PAF）的反应调控，PAF是一种常在炎症反应中产生的强效磷脂。我们在此报告，PAF可增加人类B细胞系拉莫斯（Ramos）中TNF-α基因的RNA水平。这是由转录速率的增加和TNF-α转录本较长的半衰期介导的。在这些细胞中，TNF-α基因的诱导迅速且不依赖于新的蛋白质合成。尽管PAF增加了TNF-α基因的RNA，但PAF仅在存在共刺激剂（如佛波酯（PMA））的情况下才会增加TNF-α蛋白水平。我们推测，PAF在转录水平起作用以增加TNF-α RNA，但转录后阻滞作用调节蛋白质产生。我们还报告，PAF增强了PMA诱导的人类外周血B细胞产生TNF-α的能力。这种增加在0.1微摩尔PAF时最大，并被PAF受体拮抗剂阻断。PAF调节人类B细胞细胞因子产生的能力进一步证明PAF在B细胞生物学中起作用，并表明它在涉及B细胞衍生细胞因子的病症中可能很重要。
