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1.
Innate Immun ; 28(5): 155-163, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35548957

RESUMO

Th17 cells represent important immune cells. Ursolic acid (UA) can regulate immune cell activities. This study was aimed to explore the effects of UA on Th17 cell differentiation and Schwann cell(SCs)-mediated migration and the potential mechanism. Naïve CD4+ T cells were isolated from rat peripheral blood, induced for Th17 cell differentiation, and treated with UA. The proportion of Th17 cells was detected by flow cytometry assay. SCs were co-cultured with Th17 cells. Th17 cell migration was detected by Transwell assay. The molecule expression was determined by Western blot and qRT-PCR. UA inhibited the Th17 cell differentiation and suppressed the STAT3/RORγt pathway. STAT3 overexpression up-regulated p-STAT3 and RORγt expression and promoted Th17 cell differentiation under the UA treatment. In LPS- and IFN-γ-stimulated-SCs, UA suppressed the expression of chemokines CXCL9/10, but had no significant effect of CCL20 expression. The expression CXCL9/10 receptor CXCR3 was higher in Th17 cells than that in Treg cells, while the expression CCL20 receptor CCR6 was lower in Th17 cells than that in Treg cells. UA, anti-CXCR3, and anti-CCR6 treatment inhibited SCs-mediated Th17 cell migration, and anti-CXCR3 exerted stronger inhibitory effect than Anti-CCR6. UA inhibited Th17 cell differentiation through STAT3/RORγt pathway and suppressed Th17 cell migration through down-regulating CXCL9/10 expression in SCs.


Assuntos
Quimiocina CXCL10 , Quimiocina CXCL9 , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Fator de Transcrição STAT3 , Células de Schwann , Células Th17 , Triterpenos , Animais , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Quimiocina CXCL10/biossíntese , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/biossíntese , Quimiocina CXCL9/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ratos , Fator de Transcrição STAT3/metabolismo , Células de Schwann/citologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Células Th17/citologia , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Triterpenos/farmacologia , Ácido Ursólico
2.
Free Radic Res ; 51(5): 449-459, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28554248

RESUMO

Platinum-based chemotherapy represents one of the most effective ways in combating human cancers. However, the cardiotoxicity subsequent severely limited its clinical application. Increased evidences indicate that oxidative stress plays a crucial role in the pathological process of platinum-induced cardiotoxicity. It is reported that apelin-13 a bioactive peptide has the scavenging capacity of free radical, and it has the potential to regulate the cardiovascular system. Hence, the potential of apelin-13 to antagonize cisplatin-induced cardiotoxicity was evaluated in H9c2 rat myocardial cells in vitro and in C57 mice in vivo. The results showed that cisplatin indeed caused DNA damage in H9c2 cells by promoting the accumulation of intracellular reactive oxygen species (ROS) and superoxide anion, which led to cell apoptosis and resulted in overt cardiotoxicity. However, apelin-13 pre-treatment effectively attenuated the cisplatin-induced ROS and superoxide anion generation, inhibited DNA damage, and suppressed the PARP cleavage and caspases activation. Further investigation revealed that apelin-13 blocked cisplatin-induced H9c2 cells apoptosis involving the regulation of MAPKs and PI3K/Akt signaling pathway. Importantly, apelin-13 co-treatment also significantly attenuated cisplatin-induced cardiotoxicity in vivo by inhibiting myocardial cells apoptosis and improving angiogenesis in mice heart. Taken together, our results suggest that the use of apelin-13 may be an effective strategy for antagonizing the cardiotoxicity-induced by platinum-based chemotherapy.


Assuntos
Antineoplásicos/toxicidade , Cardiotônicos/farmacologia , Cisplatino/toxicidade , Sequestradores de Radicais Livres/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Dano ao DNA , Avaliação Pré-Clínica de Medicamentos , Coração/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
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