Interleukin-11 induces intestinal epithelial cell growth arrest through effects on retinoblastoma protein phosphorylation.
Recombinant human (rh) interleukin (IL)-11 has been shown to reduce gastrointestinal mucosal injury after chemotherapy or irradiation in several animal models. As reduction of cellular proliferation can be cytoprotective, we have examined the effect of rhIL-11 compared with transforming growth factor (TGF)-beta 1 on the proliferation and cell cycle progression of a rat intestinal cell line, IEC-6. IEC-6 cells treated with rhIL-11 or rhTGF-beta 1 exhibited a reduced proliferative rate as measured by cell counts and [3H]thymidine incorporation. The presence of neutralizing anti-TGF-beta 1 antibodies did not block the antiproliferative effect of rhIL-11 indicating that the rhIL-11 activity was not mediated through the induction of endogenous TGF-beta 1 production. Growth inhibition correlated with delayed entry into S phase of the cell cycle. Cell cycle arrest was associated with suppression of retinoblastoma protein phosphorylation. Transient cell cycle arrest is a possible mechanism by which rhIL-11 may protect intestinal epithelial cells from damage induced by chemotherapy or radiation therapy. This study provides a rationale for the clinical use of rhIL-11 to preserve the integrity of the gastrointestinal mucosa during cancer treatment regimens.
Peterson
R L
RL
Department of Preclinical Research and Development, Genetics Institute, Cambridge, Massachusetts, USA.
Bozza
M M
MM
Dorner
A J
AJ
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D017370:Interleukin-11 / Q000494:pharmacology / Q000502:physiology*; D007422:Intestines / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology
D017370:Interleukin-11; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta