Pro-inflammatory cytokine interleukin-1β promotes the development of intestinal stem cells.
OBJECTIVE
We investigated the effect of IL-1β on the development of intestinal epithelial stem cells.


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.


CONCLUSIONS
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.
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Lei
L
Wang
Ziyan
Z
Liu
Yijing
Y
Li
Loretta
L
Pappan
Amy
A
Galliher-Beckley
Jishu
J
Shi
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D053583:Interleukin-1beta / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology*; D000071317:Nanog Homeobox Protein; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
C489420:Bmi1 protein, rat; D053583:Interleukin-1beta; C576179:Lgr5 protein, rat; D000071317:Nanog Homeobox Protein; C547030:Nanog protein, rat; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D051176:beta Catenin; D063150:Polycomb Repressive Complex 1