RESUMO
When exposed to gamma-rays, hair follicular cells immediately go through apoptosis, which hampers their rapid differentiation essential for the regeneration of hair. Phloroglucinol (PG) is a phenolic compound of Ecklonia cava, brown algae abundant in Jeju island, Korea. Containing plentiful polyphenols, PG is known for its instructive effects by inhibiting apoptosis, scavenging oxygen radicals, and protecting cells against oxidative stress. In this study, we demonstrate that PG rescues radiosensitive hair follicular cells from gamma radiation-induced apoptosis and DNA damage. To identify protective capacity of PG on hair follicles, we irradiated with 8.5 Gy (1.5 Gy/min) of gamma-rays to the whole body of C57BL/6 mice at day 6 after depilation with or without PG. In mice exposed to radiation, the expression of proapoptotic molecule p53 was downregulated in the skin of PG treated group. On immunohistochemical observation of the skin, PG inhibited the immunoreactivity of p53 and cleaved caspase-3. PG treatment protected hair follicular cells from cell death due to gamma-radiation. Our results suggest that PG presents radioprotective effects by inhibiting apoptosis of radiosensitive hair follicular cells and can protect hair follicular cells from gamma-ray induced damage.
Assuntos
Animais , Camundongos , Apoptose , Caspase 3 , Morte Celular , Dano ao DNA , Folículo Piloso , Remoção de Cabelo , Cabelo , Coreia (Geográfico) , Estresse Oxidativo , Phaeophyceae , Fenol , Floroglucinol , Polifenóis , Espécies Reativas de Oxigênio , Regeneração , PeleRESUMO
The immune system is specifically sensitive to oxidative stress induced by ionizing radiation because of its rapid proliferative activity. For this reason, an instructive immune system is one of the best ways to minimize side effects, such immunodeficiency, of gamma radiation. Over the past few decades, several natural plants with antioxidant and immunomodulatory properties have been identified as adjuncts for nontoxic and successful radiotherapy. Hizikia fusiforme extract (HFE) containing plentiful dietary fiber and fucoidan is known for its instructive antioxidant capacity, immunomodulation abilities, and immune activation. In this study, we determined whether HFE protects radiosensitive immune cells from gamma radiation-induced damage. C57BL/6 mice were irradiated with gamma-ray. The effect of HFE on the ionizing radiation damage of immune cells was then evaluated with an MTT assay, 3H-thymidine incorporation assay, and PI staining. We found that HFE stimulated the proliferation of gamma-ray irradiated immune cells without cytotoxic effects. We also observed that HFE not only decreased DNA damage but also reduced gamma radiation-induced apoptosis of the immune cells. Our results suggest that HFE can protect immune cells from gamma-ray damage and may serve as an effective, non-toxic radioprotective agent.
Assuntos
Animais , Camundongos , Apoptose , Fibras na Dieta , Dano ao DNA , Raios gama , Sistema Imunitário , Imunomodulação , Estresse Oxidativo , Radiação Ionizante , RadioterapiaRESUMO
Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), reflects pathophysiologic steps in MS such as the influence of T cells and antibodies reactive to the myelin sheath, and the cytotoxic effect of cytokines. Galectin-9 (Gal-9) is a member of animal lectins that plays an essential role in various biological functions. The expression of Gal-9 is significantly enhanced in MS lesions; however, its role in autoimmune disease has not been fully elucidated. To identify the role of Gal-9 in EAE, we measured changes in mRNA and protein expression of Gal-9 as EAE progressed. Expression increased with disease progression, with a sharp rise occurring at its peak. Gal-9 immunoreactivity was mainly expressed in astrocytes and microglia of the central nervous system (CNS) and macrophages of spleen. Flow cytometric analysis revealed that Gal-9+CD11b+ cells were dramatically increased in the spleen at the peak of disease. Increased expression of tumor necrosis factor (TNF)-R1 and p-Jun N-terminal kinase (JNK) was observed in the CNS of EAE mice, suggesting that TNF-R1 and p-JNK might be key regulators contributing to the expression of Gal-9 during EAE. These results suggest that identification of the relationship between Gal-9 and EAE progression is critical for better understanding Gal-9 biology in autoimmune disease.
Assuntos
Animais , Humanos , Camundongos , Anticorpos , Astrócitos , Doenças Autoimunes , Biologia , Sistema Nervoso Central , Citocinas , Progressão da Doença , Encefalomielite Autoimune Experimental , Lectinas , Macrófagos , Microglia , Modelos Animais , Esclerose Múltipla , Bainha de Mielina , Fosfotransferases , RNA Mensageiro , Baço , Linfócitos T , Fator de Necrose Tumoral alfaRESUMO
Our previous research on sulfated polysaccharide purified from Ecklonia cava, a brown alga found in Jeju island, Korea, showed that sulfated polysaccharides modulate the apoptotic threshold of intestinal cells, thereby preventing intestinal damage caused by ionizing radiation. In this study, we investigated the ability of sulfated polysaccharide to augment restoration of small intestinal stem cells from gamma-ray-induced damage. In our results, sulfated polysaccharide treatment increased the numbers of Ki-67-positive cells as well as inducible nitric oxide synthase (iNOS)-expressing cells in the small intestine compared with those of irradiated only mice. Meanwhile, exposure to irradiation increased the number of paneth cells, which are frequently associated with intestinal inflammation, whereas sulfated polysaccharide treatment reduced the number of paneth cells in the small intestinal crypt. Conclusively, our data suggest that reduction of iNOS-expressing cells and paneth cells in sulfated polysaccharide-treated mice contributes to the inhibition of radiation-induced intestinal inflammation.
Assuntos
Animais , Camundongos , Inflamação , Intestino Delgado , Coreia (Geográfico) , Óxido Nítrico Sintase Tipo II , Celulas de Paneth , Polissacarídeos , Radiação Ionizante , Células-TroncoRESUMO
The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require CD4+CD25+ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both CD4+CD25+ T cell and CD4+Foxp3+ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of CD4+CD25+ T cell and CD4+Foxp3+ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.