RESUMO
BACKGROUND/AIMS: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. METHODS: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. RESULTS: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. CONCLUSION: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.
Assuntos
Carcinoma de Células Renais/diagnóstico , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Neoplasias Renais/diagnóstico , Sistema de Sinalização das MAP Quinases , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-33/genética , Rim/metabolismo , Rim/patologia , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Regulação para CimaRESUMO
AIM: To study the expression of lymphotactin in normal kidney and renal tuberculosis and the arrangement of lymphotactin and infiltrating CD4(+) T cells and CD8(+) T cells in renal tuberculosis. METHODS: HLptn cDNA of tissues from six cases with normal kidneys and ten cases with tuberculous kidneys was amplified by RT-PCR. The RT-PCR products were separated with 2% of gel. The cDNA was cloned to vector pGM-T Easy and was completely sequenced. The immunohistochemical staining method was used to examine the expression of lymphotactin in normal kidneys and tuberculous kidneys and the expression of CD4 and CD8 in tuberculous kidneys. RESULTS: The sequence of cloned hLptn cDNA was confirmed and it was identical with the sequence of NO.U23772 published in GenBank. Both normal kidneys and tuberculous kidneys expressed hLptn mRNA. HLptn was detected not only in the cells of normal renal glomerulus and renal tubule but also in the cells of remaining renal glomerulus and renal tubule of tuberculous kidneys. The cells expressing surface antigens CD4 and CD8 scattered in granulomas. CONCLUSION: The constructive expression of hLptn is in the cells of renal glomerulus and renal tubule of normal kidney and tuberculous kidney. The accumulation of CD4(+) T cells and CD8(+) T cells in granulomas may not depend on hLptn.
Assuntos
Antígenos CD4/análise , Linfócitos T/imunologia , Tuberculose Renal/imunologia , Contagem de Linfócito CD4 , Citotoxicidade Imunológica/genética , Citotoxicidade Imunológica/imunologia , DNA Complementar/análise , Granuloma/imunologia , Granuloma/metabolismo , Fatores Imunológicos/imunologia , Tuberculose Renal/metabolismoRESUMO
AIM: To induce dendritic cells (DCs) from human peripheral blood monocytes in vitro and to investigate the kinetics lymphotactin (Lptn) mRNA expression. METHODS: Monocytes were isolated from normal human peripheral blood cells by density gradient centrifugation and the plastic-adherent cells were cultured with the cytokines (rhGM-CSF, rhIL-4, rhTNF-alpha). The immature and mature DCs' surface antigens CD1a and CD83 were analyzed by flow cytometry (FCM). The morphology of mature DCs induced by rhTNF-alpha was observed under electron microscope. Lptn cDNA was amplified by RT-PCR, cloned to vector pGM-T Easy and completely sequenced. The RT-PCR products of cells were separated on gel and analyzed by semi-quantification. RESULTS: The cells cultured for 7 d exhibited special dendritic morphology of mature DCs and highly expressed CD83. The sequence of cDNA was confirmed and was identical to that of NO. U23772 published in GenBank. The Lptn mRNA expression of DCs was stronger in DCs cultured for 7 d than in those for 5 d, whereas it was not detected in those for 3 d. CONCLUSION: The monocyte-derived dendritic cells can express Lptn mRNA in a maturation-dependent manner.