NDLI: Tumor necrosis factor alpha is an autocrine growth regulator during macrophage differentiation.

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Tumor necrosis factor alpha is an autocrine growth regulator during macrophage differentiation.

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Tumor necrosis factor alpha is an autocrine growth regulator during macrophage differentiation.

Content Provider	PubMed Central
Author	Witsell, A. L. Schook, L. B.
Abstract	Previous experiments have revealed the expression of tumor necrosis factor alpha (TNF-alpha) transcripts in all murine bone marrow-derived macrophage colonies isolated from days 5 through 9 of differentiation in vitro. These results implicated a role for TNF-alpha gene expression during macrophage differentiation. Antisense oligomers to the initiation region of the TNF-alpha message were used to inhibit its expression, thus allowing the role of TNF-alpha gene expression in controlling the differentiation of macrophages to be determined. Results showed that TNF-alpha regulated the proliferation of macrophages during differentiation. Cells isolated on day 3 were exclusively vulnerable to the effects of blocking TNF-alpha gene expression, displaying a 30% increase in proliferation over control cells or sense oligomer-treated cells. Thus, in the absence of TNF-alpha gene expression, cells maintained proliferation instead of undergoing terminal differentiation. Exogenous TNF-alpha was capable of rescuing day 3 antisense-treated cells, therefore maintaining normal levels of proliferation. In contrast, blocking interleukin 1 beta gene expression by antisense oligonucleotide treatment had no effect on proliferation. Addition of exogenous recombinant murine or human TNF-alpha decreased the total cell number 25-50% regardless of whether cells were grown in medium containing colony-stimulating factor 1 (CSF-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These results suggested that exogenous TNF-alpha suppressed proliferation of early hematopoietic progenitors, whereas endogenous TNF-alpha regulated proliferation of macrophage progenitors. The number of differentiated, adherent macrophages on day 5 of differentiation in vitro was increased by TNF-alpha treatment of GM-CSF-induced macrophages but was suppressed in CSF-1-induced macrophages. These findings suggest that distinct TNF receptor expression and/or signaling is induced in differentiating macrophages stimulated with either growth factor.
Starting Page	4754
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	89
Language	English
Publisher Date	1992-05-15
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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