Effect of tumor necrosis factor-alpha on developing optic nerve oligodendrocytes in culture.
There is increasing evidence that proinflammatory cytokines are involved in the development of periventricular leukomalacia (PVL), a condition in which developing oliodendrocytes (OLs) are preferentially injured. In the present study, we utilized an in vitro assay to demonstrate that the A2B5+ OL progenitors as well as the O4+ prooligodendrocytes (pro-OLs) were more susceptible to tumor necrosis factor-alpha (TNF-alpha) cytotoxicity than the O4+/O1+ immature OLs. OL progenitors were isolated from optic nerves of 7-day-old rat pups and cultured in chemically defined medium supplemented with platelet-derived growth factor and basic fibroblast growth factor. OL progenitors were allowed to differentiate into pro-OLs and immature OLs under special cultural conditions. Cells at three different developmental stages were subjected to TNF-alpha treatment. Cell death, presumably by apoptosis as evidenced by TUNEL staining and caspase-3 activation, was observed following TNF-alpha treatment. Corresponding to TNF-alpha-induced apoptosis, cell survival rate decreased in a time- and dose-dependent manner. The sensitivity of different OL developmental stages to TNF-alpha decreased with the progression of cell maturation. However, this differential response was not related to differentially expressed TNF-alpha receptors. Consistent with reports that progenitor cells are preferentially injured in PVL, our results may further support the role of TNF-alpha as a potential mediator of PVL.
Pang
Yi
Y
Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Cai
Zhengwei
Z
Rhodes
Philip G
PG
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D009900:Optic Nerve / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha