IL-4 Downregulates PD-L1 Level Via SOCS1 Upregulation-Induced JNK Deactivation to Enhance Antitumor Immunity in In Vitro Colorectal Cancer.

IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Interferon and Cytokine Research Pub Date : 2024-11-01 Epub Date: 2024-10-04 DOI:10.1089/jir.2024.0110
Ruiyan Huang, Baofan Zhang, Wanchun Ye, Zhongjie Tang, Qingsong Zheng
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Abstract

Interleukin-4 (IL-4) controls cell growth and immune system regulation in tumorigenesis and can inhibit the growth of colon cancer cell lines, but the possible mechanism is unclear. In this study, we investigated the possible mechanism of IL-4 in colorectal cancer (CRC) through in vitro experiments. CRC cells received treatment with IL-4 (50 ng/mL), investigating the suppressor of cytokine signaling 1 (SOCS1)-related mechanism underlying the role of IL-4 in the progression and immunosuppression of CRC. The malignant processes of CRC cells and CD8+T cell-mediated immune response in CRC cells were determined by CCK-8, Transwell, wound healing, and flow cytometry assays. Programmed death ligand 1 (PD-L1), SOCS1 expressions, and c-Jun N-terminal kinase (JNK) activation in CRC cells were analyzed by quantitative reverse transcription polymerase chain reaction and/or Western blot. IL-4 repressed the malignant processes, yet promoted the apoptosis of CRC cells. Besides, IL-4 downregulated PD-L1 level, upregulated SOCS1 level, and restrained JNK activation in CRC cells, while enhancing CRC cell-killing effect of CD8+T cells. IL-4-induced effects on the aforementioned malignant processes of CRC cells and the killing effect of CD8+T cells toward CRC cells were all reversed when SOCS1 was knocked down in the CRC cells. IL-4 downregulates PD-L1 level via SOCS1 upregulation-induced JNK deactivation to enhance antitumor immunity in in vitro CRC. The study provides a theoretical basis for the clinical application of IL-4 in antitumor immunity in CRC.

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IL-4 通过 SOCS1 上调诱导 JNK 失活下调 PD-L1 水平,增强体外结直肠癌抗肿瘤免疫力
白细胞介素-4(IL-4)在肿瘤发生过程中控制细胞生长和免疫系统调节,并能抑制结肠癌细胞株的生长,但其可能的机制尚不清楚。本研究通过体外实验研究了 IL-4 在结直肠癌(CRC)中的可能机制。CRC细胞接受IL-4(50 ng/mL)处理,研究IL-4在CRC进展和免疫抑制中发挥作用的细胞因子信号抑制因子1(SOCS1)相关机制。通过CCK-8、Transwell、伤口愈合和流式细胞术测定了CRC细胞的恶性过程和CD8+T细胞介导的免疫反应。通过定量反转录聚合酶链反应和/或 Western 印迹分析了 CRC 细胞中程序性死亡配体 1(PD-L1)、SOCS1 的表达和 c-Jun N 端激酶(JNK)的活化。结果显示,IL-4抑制了CRC细胞的恶性过程,但促进了其凋亡。此外,IL-4还能下调PD-L1水平,上调SOCS1水平,抑制JNK在CRC细胞中的激活,同时增强CD8+T细胞对CRC细胞的杀伤作用。当 CRC 细胞中的 SOCS1 被敲除时,IL-4 诱导的对 CRC 细胞上述恶性过程的影响以及 CD8+T 细胞对 CRC 细胞的杀伤作用均被逆转。IL-4通过上调SOCS1诱导的JNK失活来下调PD-L1水平,从而增强体外CRC的抗肿瘤免疫力。该研究为IL-4在CRC抗肿瘤免疫中的临床应用提供了理论依据。
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来源期刊
CiteScore
3.80
自引率
0.00%
发文量
78
审稿时长
2.2 months
期刊介绍: Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.
期刊最新文献
Dual Time-Dependent Effects of Interleukin-33 Administration on the Kidney Postmyocardial Infarction. Integrated Analysis of Noncoding RNAs (PVT-1 and miR-200c) and Their Correlation with STAT4/IL-6 Axis as Reliable Biomarkers for COVID-19 Severity. IL-4 Downregulates PD-L1 Level Via SOCS1 Upregulation-Induced JNK Deactivation to Enhance Antitumor Immunity in In Vitro Colorectal Cancer. Multifarious Aspect of Cytokines as an Immuno-Therapeutic for Various Diseases. The Impact of Chemokine-Like Receptor 1 Gene Knockout on Lipopolysaccharide-Induced Epididymo-Orchitis in Mice.
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