RESUMEN
Plasmacytoid dendritic cells (pDCs) exert dual roles in immune responses through inducing inflammation and maintaining immune tolerance. A switch of pDC phenotype from pro-inflammation to tolerance has therapeutic promise in the treatment of autoimmune diseases. Vinpocetine, a vasoactive vinca alkaloid extracted from the periwinkle plant, has recently emerged as an immunomodulatory agent. In this study, we evaluated the effect of vinpocetine on phenotype of pDCs isolated from C57BL/6 mice and explored its possible mechanism. Our data showed that vinpocetine significantly downregulated the expression of CD40, CD80, and CD86 on pDCs and increased the expression of translocator protein (TSPO), the specific receptor of vinpocetine, in pDCs. Vinpocetine significantly inhibited the Toll-like receptor 9 signaling pathway and reduced the secretion of related cytokines in pDCs through TSPO. Furthermore, viability of pDCs was significantly promoted by vinpocetine. These findings imply that vinpocetine serves as an immunomodulatory agent for pDCs and may be applied for the treatment of pDCs-related autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Factores Inmunológicos/farmacología , Alcaloides de la Vinca/farmacología , Vinca/inmunología , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Islas de CpG/genética , Citocinas/metabolismo , Células Dendríticas/inmunología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Oligodesoxirribonucleótidos/inmunología , Receptores de GABA/genética , Receptores de GABA/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 9/metabolismoRESUMEN
Catharanthus roseus G. Don. (CR) or periwinkle plants are widely grown/ cultivated as garden plants in the tropics and subtropics. In spite of its predominantly entomophilous nature, CR pollen had been reported to be airborne and allergenic. The objective of this study was to discover the seasonal changes of CR pollen concentration in air, to determine its potential to cause respiratory allergy and to analyze its allergenic components. A 2-year aerobiological survey was conducted with a Burkard 7-day sampler in an agricultural farm in the suburban zone of Calcutta city where CR pollen was found to be almost perennial with 3.6-5.4% contribution to the aeropollen load. Skin prick test was conducted on 282 respiratory allergic individuals living within a 15 km radius of the study area. 29.8% of them were positive to CR pollen. Among them, 80.9% were directly involved in gardening. The whole pollen extract was subjected to gel filtration in a Sephacryl S-200 column. Among 5 eluted fractions, fraction I showed optimum IgE-reactivity in ELISA-inhibition. The fraction I shows 4 protein components in SDS-PAGE, within which 3 (40-66 kD molecular mass) were found to be IgE-reactive in immunoblotting using patient sera. It can be concluded that CR pollen can trigger IgEmediated respiratory allergy in the people living in close proximity.