Immunology Department, "Victor Babes" National Institute of Pathology, 99-101 Spl. Independentei, 050096 Bucharest, Romania.
Faculty of Biology, University of Bucharest, 91-95 Spl. Independentei, 76201 Bucharest, Romania.
J Immunol Res. 2017;2017:9212134. doi: 10.1155/2017/9212134. Epub 2017 Nov 26.
We present the evaluation of inflammatory cytokines in mouse cutaneous melanoma experimental model, as markers of disease evolution. Moreover, to test our experimental model, we have used low doses of dacarbazine (DTIC). C57 BL/6J mouse of both sexes were subjected to experimental cutaneous melanoma and treated with low doses of DTIC. Clinical parameters and serum cytokines were followed during tumor evolution and during DTIC therapy. Cytokine/chemokine pattern was assessed using xMAP technology and the following molecules were quantified: interleukins (IL)-1-beta, IL-6, IL-10, IL-12 (p70), interferon (IFN)-gamma, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP-1), and keratinocyte-derived chemokine (KC). Significant differences were found between normal females and males mice, female mice having a statistically higher serum concentration of IL-1-beta compared to male mice, while males have a significantly higher concentration of MIP-1-alpha. During melanoma evolution in the female group, IL-1-beta, MIP-1-alpha, and KC circulatory levels were found 10-fold increased, while other cytokines doubled their values. In the male mice group, only circulatory KC increased 4 times, while IL-1-beta and TNF-alpha doubled their circulatory values. Various serum cytokines correlated with the disease evolution in cutaneous melanoma mouse model.
我们展示了炎性细胞因子在小鼠皮肤黑色素瘤实验模型中的评估,作为疾病进展的标志物。此外,为了测试我们的实验模型,我们使用了低剂量的达卡巴嗪(DTIC)。我们对 C57BL/6J 雌雄小鼠进行了皮肤黑色素瘤实验,并使用低剂量的 DTIC 进行了治疗。在肿瘤演变和 DTIC 治疗期间,我们监测了临床参数和血清细胞因子。使用 xMAP 技术评估了细胞因子/趋化因子图谱,并定量了以下分子:白细胞介素(IL)-1β、IL-6、IL-10、IL-12(p70)、干扰素(IFN)-γ、粒细胞巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子(TNF)-α、巨噬细胞炎症蛋白(MIP)-1α、单核细胞趋化蛋白(MCP)-1 和角质细胞衍生的趋化因子(KC)。我们发现正常雌性和雄性小鼠之间存在显著差异,雌性小鼠的血清 IL-1β浓度明显高于雄性小鼠,而雄性小鼠的 MIP-1α浓度明显更高。在雌性小鼠组的黑色素瘤演变过程中,我们发现 IL-1β、MIP-1-α 和 KC 的循环水平增加了 10 倍,而其他细胞因子的浓度增加了一倍。在雄性小鼠组中,只有 KC 的循环水平增加了 4 倍,而 IL-1β和 TNF-α的循环水平增加了一倍。各种血清细胞因子与皮肤黑色素瘤小鼠模型的疾病演变相关。