Zhou Yi, Lu Xiaotong, Luo Shimeng, Li Yingpei, Zhang Yuheng, Li Zuo, Zhu Zhiyuan, Shen Tong
Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, China.
Wei Sheng Yan Jiu. 2021 Sep;50(5):814-820. doi: 10.19813/j.cnki.weishengyanjiu.2021.05.018.
To investigate the effects of interleukin-17(IL-17) antibody on polarization of adipose tissue macrophages(ATM) in mice fed with high-fat diet(HFD) exposed to bisphenol A(BPA).
Four week-old male C57 BL/6 mice were divided into control group, IgG group, IL-17 antibody group, 1000 nmol/L BPA group, 1000 nmol/L BPA+IgG group, and 1000 nmol/L BPA+IL-17 antibody group according to random number table method. Eight mice per group were fed with HFD and BPA was exposed by drinking water. The IgG group and the 1000 nmol/L BPA+IgG group were intraperitoneally injected with 100 μg IgG antibody once a week, and the IL-17 group and the 1000 nmol/L BPA+IL-17 antibody group were intraperitoneally injected with 100 μg IL-17 antibody once a week. After 16 weeks, the mice were sacrificed, and serum samples were collected for serum separation. Leptin level was measured by enzyme-linked immunosorbent assay(ELISA). The expression of IL-1β, IL-6 and monocyte chemoattractant protein-1(MCP-1)inflammatory cytokines were observed by immunohistochemistry(IHC) of adipose tissue of epididymis. The activity of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)was measured by ELISA, and the proportion of M1 and M2 ATMs was measured by flow cytometry(FCM). The expression of CD11 c and CD206 mRNA was measured by qRT-PCR.
Compared with the control group, serum leptin, the expressions of inflammatory cytokines IL-6, IL-1β and MCP-1 in adipose tissue were increased in 1000 nmol/L BPA group, the proportion of M1 type ATM was increased(22.000%±0.500% vs. 31.467%±0.379%), iNOS activity was increased, CD11 c mRNA expression was increased, Arg-1 activity was decreased, CD206 mRNA expression was decreased, the differences were statistically significant(P<0.05), but the proportion of M2 type ATM was decreased insignificantly(P>0.05). There was no significant change in IgG group. Compared with 1000 nmol/L BPA group, IgG+1000 nmol/L BPA group had no significant change. In 1000 nmol/L BPA+IL-17 antibody group, serum leptin was decreased, the expressions of inflammatory factors IL-6, IL-1β and MCP-1 in adipose tissue were down-regulated, and the proportion of M1 type ATM was decreased(31.467%±0.379% vs. 22.933%±0.153%), iNOS activity was decreased, CD11 c mRNA expression was decreased, and the proportion of M2 type ATM was increased(4.847%±0.655% vs. 7.840%±0.555%), Arg-1 activity was enhanced, and CD206 mRNA expression was up-regulated, the differences were statistically significant(P<0.05).
IL-17 antibody may reduce the secretion of ATM inflammatory factors by inhibiting the polarization of ATM to M1 type, thus improving the inflammation of adipose tissue in BPA-infected HFD-fed mice.
探讨白细胞介素-17（IL-17）抗体对高脂饮食（HFD）喂养且暴露于双酚A（BPA）的小鼠脂肪组织巨噬细胞（ATM）极化的影响。
将4周龄雄性C57 BL/6小鼠按随机数字表法分为对照组、IgG组、IL-17抗体组、1000 nmol/L BPA组、1000 nmol/L BPA+IgG组和1000 nmol/L BPA+IL-17抗体组。每组8只小鼠喂以HFD并通过饮水暴露于BPA。IgG组和1000 nmol/L BPA+IgG组每周腹腔注射100 μg IgG抗体1次，IL-17组和1000 nmol/L BPA+IL-17抗体组每周腹腔注射100 μg IL-17抗体1次。16周后处死小鼠，采集血清样本进行血清分离。采用酶联免疫吸附测定（ELISA）法检测瘦素水平。通过附睾脂肪组织免疫组织化学（IHC）观察IL-1β、IL-6和单核细胞趋化蛋白-1（MCP-1）炎症细胞因子的表达。采用ELISA法检测诱导型一氧化氮合酶（iNOS）和精氨酸酶-1（Arg-1）的活性，采用流式细胞术（FCM）检测M1和M2型ATM的比例。采用qRT-PCR检测CD11 c和CD206 mRNA的表达。
与对照组相比，1000 nmol/L BPA组血清瘦素、脂肪组织中炎症细胞因子IL-6、IL-1β和MCP-1的表达增加，M1型ATM比例增加（22.000%±0.500% vs. 31.467%±0.379%），iNOS活性增加，CD11 c mRNA表达增加，Arg-1活性降低，CD206 mRNA表达降低，差异有统计学意义（P<0.05），但M2型ATM比例降低不显著（P>0.05）。IgG组无明显变化。与1000 nmol/L BPA组相比，IgG+1000 nmol/L BPA组无明显变化。在1000 nmol/L BPA+IL-17抗体组中，血清瘦素降低，脂肪组织中炎症因子IL-6、IL-1β和MCP-1的表达下调，M1型ATM比例降低（31.467%±0.379% vs. 22.933%±0.153%），iNOS活性降低，CD11 c mRNA表达降低，M2型ATM比例增加（4.847%±0.655% vs. 7.840%±0.555%），Arg-1活性增强，CD206 mRNA表达上调，差异有统计学意义（P<0.05）。
IL-17抗体可能通过抑制ATM向M1型极化来减少ATM炎症因子的分泌，从而改善BPA感染的HFD喂养小鼠的脂肪组织炎症。
