Cell cycle effects of IL-10 on malignant B-1 cells

Genes Immun. 2001 Aug;2(5):239-47. doi: 10.1038/sj.gene.6363773.

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/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • Cell Cycle* / genetics
  • Cell Cycle* / immunology
  • Clone Cells
  • Cyclins / genetics
  • Cyclins / metabolism
  • Gene Expression Regulation, Leukemic / immunology
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / pharmacology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Macromolecular Substances
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred NZB
  • Mice, Knockout
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / pharmacology
  • S Phase / genetics
  • S Phase / immunology
  • Tumor Cells, Cultured

Substances

  • Cyclins
  • Macromolecular Substances
  • Oligonucleotides, Antisense
  • Interleukin-10