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Transcriptional and post‐transcriptional regulation of GM‐CSF‐induced IL‐1β gene expression in PMN
Author(s) -
Fernandez Marilyn C.,
Walters John,
Marucha Phillip
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.59.4.598
Subject(s) - biology , cycloheximide , gene expression , messenger rna , tumor necrosis factor alpha , granulocyte macrophage colony stimulating factor , microbiology and biotechnology , granulocyte , regulation of gene expression , cytokine , interleukin , gene , endocrinology , medicine , immunology , protein biosynthesis , biochemistry
Abstract Polymorphonuclear leukocytes (PMN) play an important role in inflammation, immune responses, and tissue repair by secreting interleukin‐1β (IL‐1β). We investigated the regulation of IL‐1β gene expression in human PMN treated with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). GM‐CSF induced IL‐1β mRNA accumulation at 0.1 ng/ml and maximal induction was observed at 1 ng/ml. IL‐1β mRNA levels reached a maximum within 1–2 h after stimulation with GM‐CSF and returned to baseline levels by 4–6 h. The time course of IL‐1β mRNA induction by GM‐CSF was more protracted than previously reported for PMN stimulated with tumor necrosis factor‐α (TNF‐α, 10 ng/ml). Nuclear run‐on analysis indicated that GM‐CSF, like TNF, increases IL‐1β transcription. Kinetic studies with the RNA synthesis inhibitor, actinomycin D, showed that GM‐CSF induces stable IL‐1β mRNA. Cycloheximide enhanced the IL‐1β mRNA accumulation by GM‐CSF at the level of mRNA stabilization, but blocked IL‐1β mRNA expression by TNF. Thus, GM‐CSF increases IL‐1β message accumulation in PMN at both the transcriptional and post‐transcriptional levels by mechanisms that are different from TNF induction of IL‐1β gene expression.