Department of Urology, Technische Universität Dresden, Dresden, Germany.
UroFors Consortium (Natural Scientists in Urological Research) of the German Society of Urology, Düsseldorf, Germany.
In Vivo. 2021 Jul-Aug;35(4):1973-1977. doi: 10.21873/invivo.12465.
BACKGROUND/AIM: Proinflammatory cytokines play an essential role in the development and progression of prostate cancer (PCa). Especially interleukine (IL-)6 is involved in the development of aggressive PCa. Peripheral blood mononuclear cells (PBMC) have been reported to interact with cancer cells and subsequently lead to increased production of pro-inflammatory cytokines. However, the role of anti-nflammatory cytokines, such as IL-4 is still largely unexplored in prostate cancer. In the present study, we investigated the effects of IL-4 on PBMC co-cultured with PCa cells.
PBMC were co-culured with the PCa cell lines LNCaP and LNCaP-IL6+. To avoid cell-cell contact, cancer and immune cells were separated using cell culture inserts with a 0.4 μm pore size membrane. Cell growth was assessed using the [3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide] (MTT) assay. Cytokine levels were measured using a BD™Cytometric Bead Array.
Cell viability of LNCaP cells decreased massively when cells were co-cultured with PBMC. Pre-incubation with IL-4 could partly rescue the observed effect of cell viability of LNCaP cells co-cultured with PBMC. In contrast, cell viability of the LNCaP-IL6+ cell line was not affected when co-cultured with PBMC.
IL-4 counteracts the cytotoxic effects of PBMC on hormone-sensitive LNCaP cells and is involved in the immune escape and development of aggressive phenotypes of PCa.
背景/目的：促炎细胞因子在前列腺癌（PCa）的发展和进展中起着至关重要的作用。特别是白细胞介素（IL-）6 参与了侵袭性 PCa 的发展。据报道，外周血单核细胞（PBMC）与癌细胞相互作用，随后导致促炎细胞因子的产生增加。然而，抗炎细胞因子（如 IL-4）在前列腺癌中的作用仍在很大程度上未被探索。在本研究中，我们研究了 IL-4 对与 PCa 细胞共培养的 PBMC 的影响。
将 PBMC 与 PCa 细胞系 LNCaP 和 LNCaP-IL6+共培养。为避免细胞-细胞接触，使用具有 0.4μm 孔径膜的细胞培养插入物将癌细胞和免疫细胞分离。使用[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐]（MTT）测定法评估细胞生长。使用 BD™Cytometric Bead Array 测量细胞因子水平。
当细胞与 PBMC 共培养时，LNCaP 细胞的细胞活力大大降低。用 IL-4 预处理可以部分挽救与 PBMC 共培养的 LNCaP 细胞观察到的细胞活力降低的影响。相比之下，当与 PBMC 共培养时，LNCaP-IL6+细胞系的细胞活力不受影响。
IL-4 抵消了 PBMC 对激素敏感的 LNCaP 细胞的细胞毒性作用，并参与了 PCa 的免疫逃逸和侵袭性表型的发展。
