RESUMEN
Asthma is a common chronic inflammatory airway disease. Recent studies have reported that interleukin (IL)33 is a potential link between the airway epithelium and Th2type inflammatory responses, which are closely related to the progression of asthma. The IL33 receptor, ST2, is highly expressed in group 2 innate lymphoid cells (ILC2s), Th2 cells, mast cells, eosinophils and natural killer (NK) cells. Cnidii Fructus is a Chinese herb with a long history of use in the treatment of asthma in China. Osthole is one of the major components of Cnidii Fructus. The present study examined the antiasthmatic effects of osthole in mice and aimed to elucidate the underlying mechanisms involving the IL33/ST2 pathway. BALB/c mice were sensitized and challenged with ovalbumin and then treated with an intraperitoneal injection of osthole (25 and 50 mg/kg). Subsequently, the airway hyperresponsiveness (AHR) and inflammation of the lungs were evaluated. The amounts of IL4, IL5, IL13, interferon (IFN)γ and IL33 in the bronchoalveolar lavage fluid (BALF) were measured by Luminex assay and their mRNA levels in the lungs were measured by reverse transcriptionquantitative PCR. The histopathology of the lungs was performed with H&E, PAS and Masson's staining. The expression of ST2 in the lungs was evaluated by immunohistochemistry. The data demonstrated that osthole markedly reduced AHR and decreased the number of eosinophils and lymphocytes in BALF. It was also observed that osthole significantly inhibited the release of Th2type cytokines (IL4, IL5 and IL13) and upregulated the IFNγ level in BALF. Moreover, osthole significantly attenuated the IL33 and ST2 expression in the lungs of asthmatic mice. On the whole, osthole attenuated ovalbumininduced lung inflammation through the inhibition of IL33/ST2 signaling in an asthmatic mouse model. These results suggest that osthole is a promising target for the development of an asthma medication.
Asunto(s)
Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Cumarinas/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Proteína 1 Similar al Receptor de Interleucina-1/antagonistas & inhibidores , Interleucina-33/antagonistas & inhibidores , Pulmón/efectos de los fármacos , Fitoterapia , Transducción de Señal/efectos de los fármacos , Animales , Hiperreactividad Bronquial/inducido químicamente , Líquido del Lavado Bronquioalveolar/química , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación , Interferón gamma/biosíntesis , Interferón gamma/genética , Proteína 1 Similar al Receptor de Interleucina-1/biosíntesis , Proteína 1 Similar al Receptor de Interleucina-1/genética , Interleucina-33/biosíntesis , Interleucina-33/genética , Interleucinas/biosíntesis , Interleucinas/genética , Pulmón/metabolismo , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/toxicidad , Eosinofilia Pulmonar/inducido químicamente , Eosinofilia Pulmonar/prevención & control , ARN Mensajero/biosíntesis , Distribución AleatoriaRESUMEN
The present study aimed to investigate the antiinflammatory effect and mechanism of action of isosecotanapartholide (ISTP), isolated from Artemisia princeps Pampanini extract (APE). The effects of ISTP and APE on the proliferation of human keratinocytes following stimulation by tumor necrosis factorα/interferonγ were assessed. ISTP and APE downregulated the expression levels of signal transducer and activator of transcription1 (STAT1), and reduced interleukin33 (IL33) production. ISTP and APE inhibited the mRNA expression levels of thymus and activationregulated chemokine (TARC/CCL17) in a dosedependent manner. Western blot analysis demonstrated that ISTP and APE dosedependently inhibited protein expression levels of intercellular adhesion molecule1 and phosphorylation of STAT1. The results of the present study indicate that ISTP may inhibit TARC/CCL17 production in human epidermal keratinocytes via the STAT1 signaling pathway and may be associated with the inhibition of IL33 production. The current study indicated that ISTP is an active component in APE and may be a potential therapeutic agent for the treatment of inflammatory skin disorders.
Asunto(s)
Artemisia/química , Interleucina-33/biosíntesis , Queratinocitos/metabolismo , Extractos Vegetales/farmacología , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacos , Línea Celular , Humanos , Queratinocitos/citología , Extractos Vegetales/químicaRESUMEN
BACKGROUND: It has been reported that vitamin D has broad anti-inflammatory and immunomodulatory effects. OBJECTIVE: To evaluate the effects of vitamin D on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). METHODS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein mixed with complete Freund's adjuvant. The mice were administered with PBS or olive oil, intraperitoneally, in the control groups and vitamin D (200 ng every two days) in the treatment group, from day +3 to +30. At day 31, the mice were scarified and their spinal cords and brains were harvested. The expression of the IL-27 and IL-33 mRNA in the spinal cord was measured using real time-PCR. RESULTS: In PBS- or olive oil-treated EAE mice the expression of IL-27 P28 mRNA was significantly lower than that in the healthy control group (p<0.002). In both PBS- and olive oil-treated EAE groups, the expression of IL-27 EBI3 mRNA was also lower than that observed in the healthy group, but the differences were not significant. In vitamin D-treated EAE group, the expression of IL-27 P28 and IL-27 EBI3 were significantly higher compared with the olive oil-treated EAE groups (p<0.002 and p<0.04, respectively). The expression of IL-33 was significantly higher in PBS-or olive oil-treated EAE groups compared with healthy mice (p<0.05 and p<0.02, respectively). Vitamin D significantly decreased the expression of IL-33 compared with PBS- or olive oil-treated EAE mice (p<0.04, p<0.02, respectively). The PBS- or olive oil -treated EAE mice showed the clinical symptoms of EAE at days 9 and 10, respectively. The vitamin D-treated EAE group exhibited the symptoms at day 12 post immunization. The maximum mean clinical score and mean pathological scores were also significantly lower in vitamin D-treated EAE group, in comparison with PBS- or olive oil treated EAE mice (p<0.001). CONCLUSION: Vitamin D may modulate the expression of IL-27 and IL-33 in the spinal cord of EAE mice and also ameliorate the clinical symptoms of the disease.