Abstract
The small intestine is one of the most sensitive organs to irradiation injury, and the development of high effective radioprotectants especially with low toxicity for intestinal radiation sickness is urgently needed. Monophosphoryl lipid A (MPLA) was found to be radioprotective in our previous study, while its effect against the intestinal radiation injury remained unknown. In the present study, we firstly determined the intestinal apoptosis after irradiation injury according to the TUNEL assay. Subsequently, we adopted the immunofluorescence technique to assess the expression levels of different biomarkers including Ki67, γ-H2AX, and defensin 1 in vivo. Additionally, the inflammatory cytokines were detected by RT-PCR. Our data indicated that MPLA could protect the intestine from ionizing radiation (IR) damage through activating TLR4 signal pathway and regulating the inflammatory cytokines. This research shed new light on the protective effect of the novel TLR4 agonist MPLA against intestine detriment induced by IR.
Highlights
The small intestine is highly sensitive to ionizing radiation (IR), and intestinal damage is one of the major side effects induced by radiotherapy
The first set of questions is aimed at determining whether Monophosphoryl lipid A (MPLA) could exert radioprotective effects against intestinal injuries, for which we adopted TUNEL assay to examine the histological intestinal cell apoptosis among different groups
The data showed that IR greatly increased TUNEL signal in mouse intestinal epithelium, which was significantly reduced by MPLA in WT mice but not in TLR4-/- mice (Figures 1(a) and 1(b)), indicating that
Summary
The small intestine is highly sensitive to ionizing radiation (IR), and intestinal damage is one of the major side effects induced by radiotherapy. Novel safe and effective radioprotectants are urgently needed to mitigate the damages of IR on the small intestine. Burdelya et al reported that TLR5 agonist CBLB502 effectively mitigated gastrointestinal and haematopoietic radiation injury in both mice and monkeys [1]. Lipopolysaccharide (LPS), a classic TLR4 ligand, effectively protected intestinal injury through cyclooxygenase-2 (Cox-2) with the induction of prostaglandin E2 (PGE2) synthesis [3]. These TLR ligands are still away from
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