Abstract
Microglial activation has been suggested to be associated with the incidence of radiation-induced brain injury. The present study investigated the molecular mechanism(s) involved in radiation-induced activation of the microglia. Mouse microglial BV-2 cells were exposed to different doses of radiation. The release of inflammatory factors was evaluated by enzyme-linked immunosorbent assay and real-time reverse transcriptase polymerase chain reaction. Protein expression was determined by immunocytochemistry and immunoblotting. Microglial activation was induced by radiation [>16 Gray (Gy)]. Activated cells exhibited a stouter spherical morphology and the levels of ionized calcium-binding adapter molecule-1 and CD68 were considerably upregulated. The generation of inflammatory factors, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, toll‑like receptor 8 (TLR-8) and cyclooxygenase 2 (COX-2), was increased and peaked at either 3 or 6 h after radiation treatment. Phosphorylated γ-histone 2A, member X (γ-H2AX), which facilitates DNA double-strand breaks (DSBs), was upregulated at 3 h post-radiation treatment. This was accompanied by the nuclear translocation of the nuclear factor-κB (NF-κB) p65 subunit. Moreover, 3 h following radiation treatment, the NF-κB essential modulator (NEMO) was markedly elevated, whereas the NF-κB regulatory inhibitor-α (IκB-α) was considerably decreased. Our results demonstrate that the NF-κB signaling pathway may trigger microglial activation and release of inflammatory factors following irradiation. These findings may provide valuable insight into understanding the molecular mechanism(s) involved in brain injury induced by radiation therapy.