IL-28B对小鼠结肠炎的抑制作用及其机制研究

目的:研究IL-28B对葡聚糖硫酸钠(dextran sodium sulfate，DSS)诱导的小鼠结肠炎的作用和机制。方法:35只雄性C57BL/6小鼠随机分为对照组、DSS组以及IL-28B治疗组(1.25 μg、2.5 μg和5 μg)，每组7只。DSS组与IL-28B治疗组饮用2.5% DSS。从第3天开始，...

Inhibitory effects of IL-28B in a mouse model of colitis and its mechanism

Objective To investigate the effects of IL-28B in a mouse model of dextran sulfate sodium(DSS)-induced colitis and to analyze the possible mechanism.Methods Thirty-five male C57BL/6 mice were randomly divided into the following groups with seven mice in each group:control group,DSS group and three IL-28B groups(1.25μg,2.5μg and 5μg).The mice in the DSS group and IL-28B groups were fed with 2.5%DSS solution and from day 3,the IL-28B groups were given intraperitoneal injection of corresponding IL-28B every day and the DSS group was treated with PBS.During the experiment,the disease activity index(DAI)was evaluated daily.On day 8,the mice were sacrificed and peripheral blood,spleen,mesenteric lymph node and colon samples were collected.The colon samples were observed,measured in length and stained with HE,and histopathological scores were calculated based on HE staining.Changes of immune cells in different samples were detected by flow cytometry.ELISA was used to detect the expression of IL-12,IL-10,IL-1β,IL-6,IL-4 and IL-13 in serum and colon tissues.Results Compared with the DSS group,the IL-28B group(2.5μg)had lower DAI scores[(9.40±1.67)vs(3.50±1.73),P<0.01],less shortening of the colon[(5.16±0.61)cm vs(6.91±0.60)cm,P<0.01]and significantly lower histopathological scores[(7.33±0.58)vs(4.33±0.58),P<0.01].Moreover,compared with the DSS group,the IL-28B group(2.5μg)showed decreased macrophages in the peripheral blood[(21.39±3.21)%vs(15.63±2.98)%,P<0.05]and spleen[(3.03±0.28)%vs(2.05±0.48)%,P<0.05],and significantly increased mean fluorescence intensity of M2 macrophages in the colon[(1361.00±293.40)vs(2074.00±87.61),P<0.05].IL-12 expression in colon tissues and IL-1βexpression in serum were reduced,and IL-10,IL-4 and IL-13 expression in colon tissues was significantly increased in the IL-28B group(2.5μg)as compared with those in the DSS group[IL-12:(31.72±6.92)pg/mg vs(5.41±3.41)pg/mg;IL-1β:(48.01±16.13)pg/ml vs(12.27±6.26)pg/ml;IL-10:(184.70±46.82)pg/mg vs(444.30±157.80)pg/mg;IL-4:(2.23±0.27)pg/mg vs(3.64±0.80)pg/mg;IL-13:(11.79±0.99)pg/mg vs(22.59±1.92)pg/mg;all P<0.05].Conclusions IL-28B might alleviate the severity of acute enteritis in mice by increasing the secretion of IL-4 and IL-13,regulating macrophage differentiation and modulating the expression of inflammatory factors.