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- Title
Cell cycle effects of IL-10 on malignant B-1 cells.
- Authors
Yen Chong, S; Lin, Y-C; Czarneski, J; Zhang, M; Coffman, F; Kashanchi, F; Raveche, E
- Abstract
IL-10 is overexpressed in human chronic lymphocytic leukemia (CLL), and is an autocrine growth factor involved in the development of malignant B1 clones in NZB mice, a murine model for CLL. Antisense IL-10 oligonucleotide treatment induces apoptosis and cell cycle disruption in these cells both in vitro and in vivo. In addition, NZB IL-10 knock-out mice fail to develop the B-1 clones. Dampening of IL-10 protein production via antisense IL-10 oligonucleotide treatment is correlated with decreased p27/Kipl protein expression which results in increased cyclin D2, cyclin E and cyclin A associated kinase activity. The action of the antisense oligonucleotides is through alterations in cell cycle regulation, resulting in accelerated cell cycle progression, a G2/M block which culminates in apoptosis induction in the malignant cells. This implies that the role of IL-10 as an autocrine growth factor in malignant B-1 cells lies in its ability to inhibit apoptosis induction through the maintenance of sustainable cell cycle progression in malignant cells. Genes and Immunity (2001 ) 2, 239-247.
- Subjects
INTERLEUKIN-10; PANCREATIC beta cells; CELL cycle
- Publication
Genes & Immunity, 2001, Vol 2, Issue 5, p239
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/sj.gene.6363773