RESUMEN
Asthma is an inflammatory disease closely associated with activated T cells in the lung. Imbalances in Th1/Th2 and Treg/Th17 have been found in asthmatic patients. Ligustrazine from the Chinese herb chuanxiong has been used in China in combination with glucocorticoids to treat asthma. Previous studies have proved that ligustrazine can modulate the expression of transcription factors for Th1 (T-bet) and Th2 (Gata-3) in asthma. In the present study, ligustrazine alleviated allergic airway inflammation in a mouse asthmatic model by reducing the influx of eosinophils and neutrophils, which was mediated, at least in part, by the regulation of Th1/Th2 and Treg/Th17 via the re-balance of cytokine profiles and of ratios of transcription factors, T-bet/Gata-3 and Foxp3/RORγt, thus providing new insights into the mechanisms of action for asthma treatment with ligustrazine.
Asunto(s)
Asma/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Eosinófilos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Pirazinas/administración & dosificación , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Animales , Asma/inmunología , Células Cultivadas , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Homeostasis/efectos de los fármacos , Humanos , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Ovalbúmina/inmunología , Linfocitos T Reguladores/inmunología , Balance Th1 - Th2/efectos de los fármacos , Células Th17/inmunología , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the synthesis and secretion of endocrine hormones. To investigate the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on thyroid structure and function, 40 male Wistar rats were divided into 4 equal treatment groups and administered vehicle or one of three doses of PCB118. The experimental groups received intraperitoneal (i.p.) injection of 10, 100, or 1000µg/kg/day PCB118, 5 days per week for 13 weeks, whereas the control group was injected with corn oil (vehicle). Serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) were measured by radioimmunoassays. Histopathological and ultrastructural changes in the thyroid were observed under light microscopy and transmission electron microscopy (TEM). The mRNA expression levels of the sodium-iodide symporter (NIS) and thyroglobulin (TG) were quantified by real-time PCR. Increasing doses of PCB118 resulted in progressively lower FT3, FT4 and TSH concentrations in serum. Injection of PCB118 at all doses led to histopathological deterioration of the thyroid characterized by follicular hyperplasia and expansion, shedding of epithelial cells and fibrinoid necrosis. Follicle cells exhibited swollen or vacuolated endoplasmic reticula, as revealed by TEM. Exposure to PCB118 also caused significant decreases in NIS and TG mRNA expression levels. Chronic exposure to low-dose PCB118 and other PCB congeners may be a significant risk factor for thyroid diseases.