Preliminary Study On Mechanisms Of Beneficial Effect Of Recombinant Human Interleukin-11 On Intestinal Radiation Injury

This study was designed to observe the effect beneficial of recombinant human interleukin-11 on intestinal radiation injury and the related mechanisms responsible for it. It is expected to improve our understanding of the role rhIL-11 played in modulation of the recovery of radiation injury and to provide theoretical and experimental principles for its clinic use.After IEC-6 cells were exposed to 60Co Y -ray irradiation, we documented the effect of rhIL-11 on the cell cycle, proliferation and apoptosis by means of MTT, flow cytometry, DNA electrophoresis and Annexin-V labeling. Mice were treated by rhIL-11 before and after 8.0 Gy 60Co -ray irradiation. In these animals cell cycle and apoptosis in small intestine were examined by virtue of in situ terminal labeling, flow cytometry and DNA electrophoresis. We also observed the expression of Bax and Bcl-2 in small intestine epithelial cells and alpha-chain of IL-11 receptorin IEC-6 cells by immunohisto-chemistry and Western blotting.The results demonstrated that irradiated IEC-6 cells showed dose-dependently proliferative inhibition, G2/M block and S delay. RhIL-11 also induced proliferative inhibition and cell cycle arrest in normal IEC-6 cells. This protective effect was more conspicuous in the irradiated IEC-6 cells. On the other hand, rhIL-11 treatment after irradiation and pretreatment could significantly prevent apoptosis in the crypt cells. This result might be achieved by induced expression of Bcl-2 and declined expression of Bax. It might also lead the irradiated small intestine cells to G2/M block and increase S phase proportion significantly. RhIL-11 also evokes the expression of alpha-chain protein of IL-11 receptor in IEC-6 cells. From these results, we conclude that rhIL-11 can protect small intestine from radiation injury and accelerate the recovery of small intestinal mucosa in irradiated mice.