RESUMEN
Activation of cytokine receptors and alterations in cytokines are thought to play important roles in neuronal dysfunction and in the pathogenesis of the nervous system diseases. CXCL8 (IL-8) is a CXC chemokine with chemotactic and inflammatory properties. Chemokines control mast cell infiltration in several inflammatory diseases, including stress and neurological dysfunctions. Using isolated human umbilical cord blood-derived cultured mast cells (HUCMC) from hematopoietic stem cells CD34+, mast cells were immunologically activated with anti-IgE at concentrations of 1, 5, 10 and 20 microg/ml leading to the dose-dependent production of IL-8 (p < 0.05). The increase in IL-8 mRNA expression was also noted when the cells were treated with anti-IgE at 10 microg/ml for 6 h. Immunologically activated HUCMC provoked the generation of tryptase in a dose- and time-dependent manner. We also found increased histidine decarboxylase (HDC) expression in activated HUCMC after 6 h of incubation, a rate-limiting enzyme responsible for the generation of histamine from histidine. Taken together, these results confirm that anti-IgE-activated mast cells release inflammatory mediators including CXCL8, a CXC chemokine which regulates several biological effects of mast cells, e.g. chemoattraction, and possibly causes cell arrest.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Histidina Descarboxilasa/biosíntesis , Inmunoglobulina E/inmunología , Interleucina-8/metabolismo , Mastocitos/inmunología , Triptasas/metabolismo , Células Cultivadas , Sangre Fetal/citología , Expresión Génica/inmunología , Histidina Descarboxilasa/genética , Humanos , Microscopía Electrónica de Transmisión , ARN Mensajero , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción GenéticaRESUMEN
Mast cells are important in reactions of allergic disease and are also involved in a variety of neuroinflammatory diseases. Mast cells can be immunologically activated by IgE through their Fc receptors, as well as by neuropeptides and cytokines to secrete mediators. Here we used a human mast cell-1 (HMC-1) cell line cultured and treated with a physiological activator, anti-IgE, and a nonphysiological activator, calcium ionophore A23187, for tryptase and MCP-1 generation and transcription of histidine decarboxylase. We used quercetin, a potent antioxidant, cytoprotective and anti-inflammatory compound capable of inhibiting histamine and some cytokines released from several cell types, as an inhibitor of immunological and nonimmunological stimulus for mast cells. In this study quercetin inhibits, in a dose-response manner, tryptase and MCP-1. Moreover, using RT-PCR quercetin inhibited the transcription of histidine decarboxylase, the rate-limiting enzyme responsible for the generation of histamine from histidine, and MCP-1. Our data suggest that quercetin is an important and good candidate for reducing the release of pro-inflammatory mast cell mediators activated by physiological and nonphysiological stimulators.