Inflammatory Signature after Low Dose γ-Radiation in Mice Brain and Gut: Switch from Therapeutic Benefit to Inflammation

Abstract

Low dose y-radiation (LDIR) has been used as curative/adjuvant/palliative treatment modality for a variety of medical conditions. However, LDIR has been casually linked to NFκB activation and inflammation. Here, we investigated the kinetics of cyto/chemokines and their influence on inflammation in normal tissues after LDIR. C57BL/6 mice exposed to LDIR (2–50cGy) and sacrificed after 1 h-8 days were examined for alterations in 95 cyto/chemokines in brain and gut (QPCR profiling) and selectively validated by assessing secreted levels (ELISA). Kinetics of LDIR-induced inflammation was assessed using DNA fragmentation and histomorphological changes in brain and gut. LDIR induced a dose-dependent upregulation of cyto/chemokines after 2–50cGy in both brain and gut. Two genes, Csf3 and Tnfa, were upregulated in a ‘dose- and tissue-independent’ manner. Transcriptional kinetics revealed induction of more genes both in brain and gut in early response time (1–48 h) after LDIR. Conversely, only few genes upregulated and more genes downregulated in these tissues after extended response (4–8 days) period. DNA fragmentation and histomorphological analysis revealed consistent dose-, time-and tissue-dependent inflammation after LDIR. Also, serum levels of TNF-α, VEGFA, IFN-γ, GM-CSF, MCP-1 reinstigates the inflammatory signature after LDIR. Together, these results suggest that LDIR significantly inflicts a dose- and tissue-dependent inflammation in normal tissues and this induced inflammation may equivocate over-time and, hence frequency of LDIR use may control the switch from therapeutic benefit to inflammatory response.