Cell cycle effects of IL-10 on malignant B-1 cells.
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/Kip1 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.
Yen Chong
S
S
Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, NJ 07109, USA.
Lin
Y C
YC
Czarneski
J
J
Zhang
M
M
Coffman
F
F
Kashanchi
F
F
Raveche
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology*; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016196:S Phase / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
D016213:Cyclins; D046911:Macromolecular Substances; D016376:Oligonucleotides, Antisense; D016753:Interleukin-10