RESUMEN
PU.1 is a hematopoietic cell-specific transcription factor. In the current study, we investigated the role of PU.1 in the gene expression and the function of mouse mast cells (MCs) in vitro and in vivo. When PU.1 siRNA was introduced into bone marrow-derived MCs (BMMCs), IgE-mediated activation was reduced, and the Syk and FcεRIß mRNA levels were significantly decreased. As the regulatory mechanism of the Syk gene is largely unknown, we performed promoter analysis and found that PU.1 transactivated the Syk promoter through direct binding to a cis-element in the 5'-untranslated region. The involvement of PU.1 in the Syk promoter was also observed in mouse dendritic cells and human MCs, suggesting that the relationship between PU.1 and Syk is common in mammals and in hematopoietic lineages. When antigen was administrated intravenously after the transfusion of siRNA-transfected BMMCs in the mouse footpad, the footpad thickening was significantly suppressed by PU.1 knockdown. Finally, administration of the immunomodulator pomalidomide suppressed passive systemic anaphylaxis of mice. Taken together, these results indicate that PU.1 knockdown might be an efficacious strategy for the prevention of MC-mediated allergic diseases.
Asunto(s)
Mastocitos/metabolismo , Proteínas Proto-Oncogénicas/genética , Transactivadores/genética , Anafilaxia/tratamiento farmacológico , Anafilaxia/metabolismo , Animales , Células Cultivadas , Células Dendríticas/metabolismo , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Mastocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas/metabolismo , Receptores de IgE/genética , Receptores de IgE/metabolismo , Quinasa Syk/genética , Quinasa Syk/metabolismo , Talidomida/análogos & derivados , Talidomida/farmacología , Talidomida/uso terapéutico , Transactivadores/metabolismoRESUMEN
Caterpillar hairs are thought to act as a physical barrier against natural enemies, including parasitoids. However, very few studies have experimentally demonstrated how hairs protect caterpillars from parasitoid oviposition. To clarify the importance of caterpillar hairs as an anti-parasitoid defence, we observed the generalist endoparasitoid Meteorus pulchricornis (Hymenoptera: Braconidae) attacking both smooth and hairy caterpillars under laboratory conditions. A female Meteorus pulchricornis uses its ovipositor to inject venom and lay a single egg inside host larvae. We placed a smooth Spodoptera litura (Lepidoptera: Noctuidae) caterpillar or a hairy Lymantria dispar japonica (Lepidoptera: Erebidae) caterpillar in front of parasitoid females. We observed that 100 % and 84 % of the parasitoids could successfully stab their ovipositors into the smooth larvae of S. litura and first instars of the hairy caterpillar L. dispar japonica, respectively. However, only 24 % of parasitoids could successfully stab their ovipositors into second-instar L. dispar japonica. A higher rate of successful stabs (94 %) by parasitoids was obtained by cutting the hairs of second instar L. dispar japonica much shorter than the parasitoid ovipositor. The results demonstrate that the long, thick hairs of second and later instars of L. dispar japonica function as a physical barrier against parasitoid oviposition.
