RESUMO
Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g.HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A2 (cPLA2) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii) on allergic liver injury using T.g.HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii-induced allergic acute liver injury. The results showed that ARC suppressed the T.g.HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g.HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA2, PAF, and interferon-γ. This result suggested that ARC ameliorates T.g.HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g.HSP70-induced allergic liver injury.
Assuntos
Toxoplasma , Toxoplasmose , Animais , Camundongos , Toxoplasma/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Ativação de Plaquetas , Toxoplasmose/tratamento farmacológico , Proteínas de Choque Térmico HSP70/metabolismo , Fígado/metabolismo , Fosfolipases/metabolismoRESUMO
Nonimmediate hypersensitivity to drugs has a huge diversity of clinical presentations affecting exclusively or predominantly a single organ (most often the skin) or multiple organs. The latter is the rule with drug reaction with eosinophilia and systemic symptoms, and with drug-induced vasculitis. The management includes a dozen successive steps. Finally, the patient should be provided clear information on the suspected cause of the reaction, recommendations for follow-up after severe reactions associated with a risk of sequelae, and clear recommendations for future use of medications. Pharmacovigilance networks should be informed.