Regulation of cytokine and growth factor gene expression in human bone marrow stromal cells transformed with simian virus 40.

作者：JL Slack, John Nemunaitis, DF d Andrews, Jack W. Singer · 发表于：PubMed · 年份：1990 · 被引用次数：33 · 研究领域：Virus-based gene therapy research、Hematopoietic Stem Cell Transplantation、Neonatal Respiratory Health Research

Marrow stromal cells are thought to regulate hematopoiesis by producing colony-stimulating factors (CSFs) and other cytokines, either constitutively or in response to mediators such as interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF alpha). The mechanisms by which these inflammatory cytokines induce CSF expression in stromal cells are not fully defined. In this study, we used human marrow stromal cells transformed by simian virus 40 (SV-MSCs) to study growth factor and cytokine gene regulation in response to IL-1 alpha and TNF alpha. IL-1 alpha induced significant and prolonged increases in steady-state mRNA levels for interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), granulocyte-macrophage CSF (GM-CSF), and, to a lesser extent, granulocyte-CSF (G-CSF); this induction was not dependent on new protein synthesis. Nuclear run-on analyses showed that IL-1 alpha transcriptionally activated the genes for IL-6, GM-CSF, and IL-1 beta, while TNF alpha transcriptionally induced expression of IL-6 and IL-1 beta. Furthermore, mRNA for IL-6 and IL-1 beta was dramatically superinduced by the combination of cycloheximide and TNF alpha. When SV-MSCs were cultured in semisolid medium, they formed colonies of blast-like cells that, when replated on plastic, resumed adherent growth. These "colony-derived" cell lines, unlike the parental SV-MSCs from which they were derived, constitutively expressed colony-stimulating activity and mRNA for GM-CSF, G-CSF, IL-6, and IL-1 b...