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在小鼠结肠癌细胞中表达的小鼠白细胞介素-23的抗肿瘤活性和免疫增强作用。

Antitumor activity and immune enhancement of murine interleukin-23 expressed in murine colon carcinoma cells.

作者信息

Shan Bao En, Hao Jing Sheng, Li Qiao Xia, Tagawa Masatoshi

机构信息

Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

Cell Mol Immunol. 2006 Feb;3(1):47-52.

Abstract

Interleukin (IL)-23, a cytokine composed of p19 and the p40 subunit of IL-12, can enhance the proliferation of memory T cells and production of IFN-gamma from activated T cells. It can also induce antitumor effects in murine model. To further evaluate the antitumor activity and immune enhancement of IL-23 in vivo, murine colon carcinoma cells retrovirally transduced with mIL-23 gene were injected subcutaneously (s.c.) into BALB/c mice. Survival time and tumor volume were observed. LDH release assay, [3H]-TdR incorporation assay and ELISA were used to determine CTL activity, proliferation of splenocytes and level of cytokines, respectively. Number of dendritic cells (DCs) was analyzed by flow cytometry (FCM). IL-23 secreted by Colon26/IL-23 cells suppressed the growth of tumor and prolonged the survival time of mice, enhanced proliferation of splenocytes, CTL activity, and number of DCs. IL-23 also promoted the production of Th1 cytokines such as IFN-gamma, IL-12 and TNF-alpha. However, the level of IL-4 was not enhanced significantly. These data suggested that IL-23 secreted by tumor cells can induce antitumor activity by enhancing immune response.

摘要

白细胞介素(IL)-23是一种由p19和IL-12的p40亚基组成的细胞因子,可增强记忆T细胞的增殖以及活化T细胞产生γ干扰素。它在小鼠模型中也能诱导抗肿瘤作用。为了进一步评估IL-23在体内的抗肿瘤活性和免疫增强作用,将用mIL-23基因逆转录病毒转导的小鼠结肠癌细胞皮下注射到BALB/c小鼠体内。观察生存时间和肿瘤体积。分别用乳酸脱氢酶(LDH)释放试验、[3H]-胸腺嘧啶核苷(TdR)掺入试验和酶联免疫吸附测定(ELISA)来测定细胞毒性T淋巴细胞(CTL)活性、脾细胞增殖和细胞因子水平。通过流式细胞术(FCM)分析树突状细胞(DC)的数量。Colon26/IL-23细胞分泌的IL-23抑制肿瘤生长,延长小鼠生存时间,增强脾细胞增殖、CTL活性和DC数量。IL-23还促进Th1细胞因子如γ干扰素、IL-12和肿瘤坏死因子-α(TNF-α)的产生。然而,IL-4水平没有明显升高。这些数据表明肿瘤细胞分泌的IL-23可通过增强免疫反应诱导抗肿瘤活性。

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