The Protective Role of Interleukin-11 Against Neutron Radiation Injury in Mouse Intestines via MEK/ERK and PI3K/Akt Dependent Pathways

Abstract

Neutron irradiation (IR) has been proven to cause more serious damage than gamma IR. Preventing and curing neutron IR damage remains an urgent issue. The objective of this study was to investigate the radioprotective effects of IL-11 against neutron IR-induced damage in small intestine of mice. Mice were exposed to 3-Gy neutron IR whole body and then treated with 500 μg/kg interleukin-11 (IL-11) intraperitoneally every day. Mice were observed at various time-points over 1-5 days after IR. IEC-6 cells were exposed to 4 Gy neutron IR, and 100 ng/mL rhIL-11 was added to culture medium. Cell proliferation activity was estimated by MTT assay and rates of apoptosis were estimated by flow cytometry. IL-11 slightly alleviated the incidence of diarrhea in the mice and promoted intestinal epithelia regeneration. In the in vitro study, neutron IR activated extracellular signal-regulated kinase (ERK)1/2 phosphorylation in intestinal epithelial cells constitutively, which was initially suppressed and then activated later by IL-11. The MEK-specific inhibitor U0126 could antagonize the positive effect of IL-11 on cell growth. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway activation was suppressed after neutron IR, but could be triggered by IL-11 to protect the cells. The PI3K inhibitor LY294002 suppressed the positive effect of IL-11 on cell growth, and antagonized the protective effect of IL-11 against cell death after neutron IR. IL-11 increases cell proliferation after neutron IR in MEK and PI3K-dependent signaling pathways, but protects cells against death only in the PI3K-dependent signaling pathway.