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Human pro-IL-1 beta gene expression in monocytic cells is regulated by two distinct pathways.

作者:Matthew J. Fenton, Mary W. Vermeulen, Burton D. Clark, Andrew C. Webb, Philip E. Auron · 发表于:The Journal of Immunology · 年份:1988 · DOI:10.4049/jimmunol.140.7.2267 · 被引用次数:204 · 研究领域:Immune Response and Inflammation、RNA Research and Splicing、Cytokine Signaling Pathways and Interactions

We have previously reported that the pro-IL-1 beta gene is transiently expressed in THP-1 human monocytic leukemia cells after stimulation with bacterial LPS. Herein we show differential pro-IL-1 beta gene transcription in the same cell type using two distinct stimuli. This transcriptional difference is also reflected at the level of intracellular IL-1 beta protein production. In contrast to LPS, a phorbol ester (PMA) induces a stable, non-transient population of mRNA. Furthermore, each induction pathway is operational under conditions where the other is inhibited, suggesting functional independence. Evidence is presented for post-transcriptional regulation of the two responses in THP-1 cells at the level of mRNA stability. We also demonstrate a similar dualistic response in primary monocyte-derived human macrophages as well as the human myelocytic cell line HL-60.