Interleukin-1 Regulates Proliferation and Differentiation of Oligodendrocyte Progenitor Cells

• Published in: Molecular and cellular neuroscience Vol. 20; no. 3; pp. 489 - 502
• Main Authors: Vela, José M., Molina-Holgado, Eduardo, Arévalo-Martı́n, Ángel, Almazán, Guillermina, Guaza, Carmen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2002
• Subjects: Animals; Animals, Newborn; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Division - drug effects; Cell Division - physiology; Cells, Cultured; Humans; Interleukin-1 - physiology; Mice; Oligodendroglia - cytology; Oligodendroglia - drug effects; Oligodendroglia - metabolism; Rats; Receptors, Interleukin-1 - antagonists & inhibitors; Receptors, Interleukin-1 - biosynthesis; RNA, Messenger - biosynthesis; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1006/mcne.2002.1127

Interleukin-1 (IL-1) is a pleiotropic cytokine expressed during normal CNS development and in inflammatory demyelinating diseases, but remarkably little is known about its effect on oligodendroglial cells. In this study we explored the role of IL-1β in oligodendrocyte progenitors and differentiated oligodendrocytes. The effects of IL-1β were compared to those of IL-1 receptor antagonist, the specific inhibitor of IL-1 activity, since progenitors and differentiated oligodendrocytes produce IL-1β and express IL-1 receptors. Unlike other proinflammatory cytokines (TNFα and IFNγ), IL-1β was not toxic for oligodendrocyte lineage cells. However, this cytokine inhibited proliferation of oligodendrocyte progenitors in the presence of growth factors (PDGF plus bFGF). This was evidenced by a significant decrease in both cells incorporating bromodeoxyuridine (45%) and total cell numbers (57%) after 6 days of treatment. Interestingly, IL-1β blocked proliferation at the late progenitor/prooligodendrocyte (O4+) stage but did not affect proliferation of early progenitors (A2B5+). Inhibition of proliferation paralleled with promotion of differentiation, as revealed by the increased percentage of R-mab+ cells (6.7-fold). Moreover, when oligodendrocyte progenitors were allowed to differentiate in the absence of growth factors, treatment with IL-1β promoted maturation to the MBP+ stage (4.2-fold) and survival of differentiating oligodendrocytes (2.1-fold). Regarding intracellular signaling, IL-1β activated the p38 mitogen-activated protein kinase (MAPK) but not the p42/p44 MAPK and, when combined with growth factors, intensified p38 activation but inhibited the growth-factor-induced p42/p44 activation. IL-1β also induced a time-dependent inhibition of PFGF-Rα gene expression. These results support a role for IL-1β in promoting mitotic arrest and differentiation of oligodendrocyte progenitors as well as maturation and survival of differentiating oligodendrocytes.