This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Feldhaus, B. Articles by Berger, R. Search for Related Content PubMed PubMed Citation Articles by Feldhaus, B. Articles by Dietzel, I. D. Articles by Heumann, R. Articles by Berger, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Social Bookmarking                         What's this?

Effects of Interferon- and Tumor Necrosis Factor- on Survival and Differentiation of Oligodendrocyte Progenitors

Irmgard D. Dietzel, PhD

Rolf Heumann, PhD

Departments of Obstetrics and Gynecology, and Molecular Neurochemistry, University of Bochum, Bochum, Germany

Richard Berger, MD, PhD

Departments of Obstetrics and Gynecology, and Molecular Neurochemistry, University of Bochum, Bochum, Germany; Universitäts-frauenklinik, Knappschaftskrankenhaus, In der Schornau 23 - 25, D-44892, Bochum, Germany; richard.berger{at}ruhr-uni-bochum.de

Objective: There is strong evidence from recent clinical studies that ascending intrauterine infection is associated with an increased incidence of periventricular leukomalacia in very premature fetuses. Periventricular leukomalacia is characterized by disrupted myelination from a loss of oligodendrocyte progenitors. We investigated the effects of proinflammatory cytokines on the survival and differentiation of this cell type.

Methods: Cultures of more than 90% A2B5-positive progenitors were prepared from neonatal rats and kept for 3 days in medium supplemented with factors that stimulate cell proliferation. After 1 day in proliferation medium, cells were treated with interferon- (100 U/mL) and tumor necrosis factor- (100 ng/mL) for 48 hours triggering an increase in apoptotic A2B5 progenitor cells from 3.2 ± 2.3% to 11.0 ± 2.6%. After cytokine treatment cultures were transferred to medium containing factors to promote differentiation of progenitors into the myelinating phenotype.

Results: In cytokine pretreated cultures, only 2.6 ± 1.1% of total cells survived after a total of 9 days in vitro, whereas in untreated cultures most cells differentiated as shown by expression of myelin basic protein, myelin-associated glycoprotein, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and myelin oligodendrocyte-specific protein. Using ten-fold reduced concentrations of combined interferon- (10 U/mL) and tumor necrosis factor- (10 ng/mL) pretreatment resulted in a survival to 11.2 ± 4.9% of total cells with 36.3 ± 11.6% A2B5-positive cells at day 9. This indicates a major enrichment of undifferentiated cells compared with untreated controls which harbored only 1.0 ± 0.3% A2B5-positive cells.

Conclusion: Inflammatory cytokines not only induced apoptotic cell death but also prevented the differentiation of immature A2B5 oligodendrocyte progenitors into the myelinating phenotype.

Key Words: Cytokines • apoptosis • periventricular leukomalacia • fetus • intrauterine infection • oligodendrocyte precursors

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 2, 89-96 (2004)
DOI: 10.1016/j.jsgi.2003.08.004


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				W. Lin, H. P. Harding, D. Ron, and B. Popko Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-{gamma} J. Cell Biol., May 23, 2005; 169(4): 603 - 612. [Abstract] [Full Text] [PDF]