NF-κB signaling modulates radiation-induced microglial activation

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.

Shenqi Fuzheng Injection attenuates irradiation-induced brain injury in mice via inhibition of the NF-κB signaling pathway and microglial activation

“…Radiation-induced brain injury (RIBI) remains a common and severe side effect, and approximately 50% of all survivors may develop lateonset radiation-induced injury of normal brain tissues [1,[4][5][6][7] , which includes the progressive impairment of cognitive functions. Many pre-clinical studies have demonstrated that inflammatory responses tend to occur after CRT and may contribute to RIBI [8][9][10] , which suggests that neuro-inflammation is implicated in RIBI [11][12][13] .…”

“…These findings suggest that irradiation-induced microglial activation may play an important part in RIBI. In vitro studies have shown that irradiation could induce microglial activation, which, in turn, led to elevated expression of a variety of proinflammatory genes, including IL-1β, IL-6, TNF-α, and COX-2 [11] .…”

Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia

“…5 a). In addition, previous studies proved that the inflammatory state of microglia after IR activation was related to distinct signaling pathways, such as the NF-κB and MAPK pathways [ 26 , 27 ]. Therefore, selective pharmacological inhibitors of the NF-κB pathway (Bay-11-7082) and the three main branches of MAPK pathway, including SP600125 (c-Jun N-terminal kinase, JNK), U0126 (extracellular signal-regulated kinase, ERK), and SB203580 (p38) were used to detect the possible pathways that act on the expression of the two selected RILs.…”

MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo

“…MG132 inhibits NF-κB activation by irradiation. NF-κB is a crucial transcription factor that regulates the expression of genes linked to apoptosis, survival, proliferation, invasion, metastasis and tumor cell transformation (17,18). NF-κB has been extensively reported to be implicated in cancer cell radiosensitivity due to their role of transcriptional regulation upon radiation exposure.…”