Characterization and Regulation of Insulin-Like Growth Factor-Imrna Transcripts in Myeloid Cells
Arkins, John Francis
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https://hdl.handle.net/2142/72213
Description
Title
Characterization and Regulation of Insulin-Like Growth Factor-Imrna Transcripts in Myeloid Cells
Author(s)
Arkins, John Francis
Issue Date
1992
Doctoral Committee Chair(s)
Kelley, Keith W.
Department of Study
Animal Sciences
Discipline
Animal Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Molecular
Biology, Cell
Health Sciences, Immunology
Abstract
Using reverse transcription and PCR amplification, cDNA fragments corresponding to IGF-I Ea and Eb mRNA transcripts were detected in all murine immune cell types. The identity of these sequences was confirmed by cloning and sequencing. Macrophages had 20 to 40 fold higher levels of IGF-I mRNA than B or T cells and macrophage transcripts initiated exclusively within exon 1, characteristic of extra-hepatic tissues. Surprisingly, macrophage IGF-I mRNA transcripts contained a proportion of IGF-I Eb transcripts which was equal to, or greater than, that produced by the liver. A large molecular weight IGF-I precursor, was detected in macrophage lysates by Western blotting.
In-vitro differentiation of bone marrow cells to a macrophage phenotype with colony-stimulating factor-1 (CSF-1) resulted in as much as one-thousand fold increases in IGF-I mRNA levels. This coordinate induction of IGF-I transcription was accompanied by a decrease in steady state levels of IGF-I receptor mRNA. IGF-II transcripts were not detected in any immune cell type. Single and multilineage CSFs were used to demonstrate that the induction of IGF-I transcription was a general feature of myeloid cell differentiation but macrophage cell types expressed particularly high levels of IGF-I mRNA. Exogenous IGF-I supported the proliferation of bone marrow progenitors undergoing differentiation in-vitro in the presence of one of a number of colony stimulating factors. Insulin-like growth factor binding protein-3 (IGFBP-3) inhibited the proliferation of differentiating bone marrow progenitors and this inhibition could be reversed by the addition of exogenous IGF-I. Interferon-$\gamma$ induced a time and dose-dependent down-regulation of IGF-I mRNA levels in differentiating and mature macrophage populations by inhibiting gene transcription. This down-regulation was dependent on protein synthesis. These results suggest that IGF-I acts as an autocrine growth factor, supporting the proliferation and differentiation of myeloid progenitors.
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