RESUMO
Despite strong evidence supporting the cellular interplay between haemostasis and innate immunity, humoral connections between blood coagulation and the behavior of inflammatory macrophages are not well understood. In this study, we investigated changes in gene expression of selected cytokines and chemokines and their secretion profiles following thrombin stimulation of murine macrophages. Thrombin promoted differentiation of macrophages into an M1-like phenotype that was associated with the expression of classical pro-inflammatory markers. The cellular actions of thrombin on macrophages were mediated in part by protease-activated receptor-1 (PAR-1) and were dependent on phosphoinositide 3-kinase/AKT and nuclear factor-κB. Moreover, heat-denatured thrombin stimulated the secretion of some pro-inflammatory mediators to the same magnitude indicating that different receptors transmit cellular signals of enzymatically active thrombin and nonactive thrombin, the latter remaining so far undefined. Finally, pretreatment of macrophages with thrombin resulted in tolerance against secondary stimulation by lipopolysaccharide with regard to expression of tumor necrosis factor-α. These results provide new insights into the molecular link between the key enzyme of haemostasis and innate immunity responses.
Assuntos
Inflamação/metabolismo , Macrófagos/metabolismo , Trombina/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/patologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptor PAR-1/genética , Células Th1/imunologia , Trombina/imunologiaRESUMO
Con el objeto de demostrar la acción preventiva del ketotifeno en relación al asma, se realizó un ensayo controlado y doble-ciego en el cual se incluyeron 51 niños con el diagnóstico de asma extrínseca tipo l de intensidad leve y moderada. Un grupo de niños recibió ketotifeno + teofilinato de colina y otro grupo recibio placebo + teofilinato de colina (5 mgs./kg. peso/cada 6 horas). En el grupo que recibió ketotifeno se observó una mejoria progresiva de los síntomas a partir de la 3ra. semana de tratamiento, siendo esta mejoría estadísticamente significativa (P<0,001) en comparación con el grupo control. Además, se observó una reducción importante de los efectos secundarios de la teofilina
