Pro-inflammatory cytokine interleukin-1β promotes the development of intestinal stem cells

Inflamm Res. 2012 Oct;61(10):1085-92. doi: 10.1007/s00011-012-0501-3. Epub 2012 Jun 16.

Abstract

Objective: We investigated the effect of IL-1β on the development of intestinal epithelial stem cells.

Materials and methods: Normal intestinal epithelial cell line IEC-18 cells were cultured in the presence or absence of 200 pM of IL-1β in serum-free medium (SFM) for various time periods. The effects of IL-1β on intestinal stem cell self-renewal and IEC-18 cell proliferation were evaluated by a colony formation assay, MTT assay, and a focus formation assay. The expression of stemness genes including Bmi-1, Lgr-5, c-myc, Nanog, and β-catenin in IEC-18 cells were measured by quantitative PCR and western blot analysis.

Results: IEC-18 cells grew as a monolayer in SFM in the absence of IL-1β. Cellular spheres were formed when IEC-18 cells were grown in SFM in the presence of IL-1β. IL-1β induced the development of large colonies in the soft-agar as well as the formation of foci when IEC-18 cells were cultured in type-I collagen-coated plates. The expression of Bmi-1, Lgr-5, c-myc, Nanog, and β-catenin were significantly increased in IEC-18 cells treated with IL-1β.

Conclusion: Our studies provide direct evidence the IL-1β may play an important role in the self-renewal of intestinal epithelial stem cells and the development of cancer stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Interleukin-1beta / pharmacology*
  • Intestines / cytology*
  • Nanog Homeobox Protein
  • Polycomb Repressive Complex 1 / genetics
  • Proto-Oncogene Proteins c-myb / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, G-Protein-Coupled / genetics
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Transcription Factors / genetics
  • beta Catenin / genetics

Substances

  • Bmi1 protein, rat
  • Interleukin-1beta
  • Lgr5 protein, rat
  • Nanog Homeobox Protein
  • Nanog protein, rat
  • Proto-Oncogene Proteins c-myb
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Transcription Factors
  • beta Catenin
  • Polycomb Repressive Complex 1