ABSTRACT
Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the effects of phlorofucofuroeckol B (PFF-B) isolated from Ecklonia stolonifera, on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated microglia. PFF-B decreased secretion of pro-inflammatory cytokines including tumor necrosis factor α, interleukin (IL)-1ß, and IL-6 and the expression of pro-inflammatory proteins such as cyclooxygenase-2 and inducible nitric oxide synthase in LPS-stimulated BV-2 cells. Profoundly, PFF-B inhibited activation of nuclear factor kappaB (NF-κB) by preventing the degradation of inhibitor κB-α (IκB-α), which led to prevent the nuclear translocation of p65 NF-κB subunit. Moreover, PFF-B inhibited the phosphorylation of Akt, ERK, and JNK. These results indicate that the anti-inflammatory effect of PFF-B on LPS-stimulated microglial cells is mainly regulated by the inhibition of IκB-α/NF-κB and Akt/ERK/JNK pathways. Our study suggests that PFF-B can be considered as a therapeutic agent against neuroinflammation by inhibiting microglial activation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzofurans/pharmacology , Dioxins/pharmacology , Immunosuppressive Agents/pharmacology , Microglia/drug effects , NF-kappa B/metabolism , Animals , Benzofurans/isolation & purification , Cell Line , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Dioxins/isolation & purification , Down-Regulation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Inflammation Mediators/metabolism , Lipopolysaccharides/immunology , MAP Kinase Kinase 4/metabolism , Mice , Microglia/cytology , Microglia/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Oncogene Protein v-akt/metabolism , Phaeophyceae/immunology , Signal Transduction/drug effects , Transcriptional Activation/drug effectsABSTRACT
OBJECTIVE: In our previous study, repeated irradiations showed persistent depression of immune response, especially Th1-related immune response. Here, we hypothesized and determined that irradiation may exacerbate development of allergic airway inflammation. METHODS: C57BL/6 mice were irradiated repeatedly at 1 Gy or 0.5 Gy. At 6 months after irradiation, mice were sensitized and challenged short-term with OVA. Antigen-specific immunoglobulins, the percentages of inflammatory cells, chemokine expression, cytokine levels, and collagen deposition were tested. RESULTS: In irradiated mice, IgG2a in serum was lower when compared with that of control mice, while IgG1 was significantly higher. Interestingly, the percentages of macrophages in bronchoalveolar lavage fluid (BALF) and the lung of irradiated mice were significantly higher. Conversely, the percentages of neutrophil were significantly lower in BALF of irradiated mice. In the lung of irradiated mice, MCP-1 and IP-10 for attraction of macrophages showed the higher expression level, but KC expression for neutrophils showed no difference. Next, TGF-ß1 and IL-17A in BALF were higher in irradiated mice. In addition, phosphorylated-Smad2/3 was increased in irradiated mice. Finally, the deposition of collagen was increased in irradiated mice. CONCLUSION: Our study showed that fractionated irradiation lead to the chronic allergic airway inflammation through increasing the influx of macrophages and active TGF-ß levels.
Subject(s)
Asthma/etiology , Dose Fractionation, Radiation , Macrophages/radiation effects , Animals , Chronic Disease , Collagen/metabolism , Female , Immunoglobulin E/biosynthesis , Immunoglobulin G/biosynthesis , Interferon-gamma/analysis , Interleukin-17/analysis , Interleukin-4/analysis , Macrophages/physiology , Mice , Mice, Inbred C57BL , Transforming Growth Factor beta1/physiologyABSTRACT
Globally, there are concerns over the risks associated with radiation exposure, so it is important to understand the biological effects of radiation exposure. Driven by the need to detect the presence of radiation exposure, biomarkers to monitor potential exposure after radiological accidents can be developed and would be extremely valuable for biological response. In this study, the behavior of spermidine as a biomarker was investigated in a C57BL/6 mouse model exposed to an acute whole-body sublethal dose of 6 Gy. The spermidine content values in serum increased for up to two days after 6 Gy irradiation. However, the enhanced spermidine content observed on day +3 in irradiated mice returned to normal levels on the subsequent five days. The result indicates that spermidine can be used as a biomarker of biological response to radiation exposure.
