脂肪间充质干细胞促进M1型巨噬细胞向M2型巨噬细胞转化  

Adipose-derived stem cells promote the polarization from M1 macrophages to M2 macrophages

作　　者：尹学红[1] 庞春燕[1] 白力[1] 张颖[1] 耿立霞[1] 

机构地区：[1]包头医学院第一附属医院,内蒙古包头014040

出　　处：《细胞与分子免疫学杂志》2016年第3期332-338,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81450040);内蒙古自治区自然科学基金(2014MS0353);内蒙古自治区高等学校科学研究项目(NJZY13248)

摘　　要：目的探索脂肪间充质干细胞(ADSC)对M1/M2型巨噬细胞的影响以及ADSC能否促使M1型巨噬细胞向M2型巨噬细胞转化。方法利用脂多糖(LPS)、γ干扰素(IFN-γ)刺激J774.1巨噬细胞24 h诱导为M1型巨噬细胞,利用白细胞介素4(IL-4)刺激J774.1巨噬细胞24 h诱导为M2型巨噬细胞;将M1/M2型巨噬细胞分别与ADSC共培养24 h后,收集巨噬细胞和上清液,用实时定量PCR和ELISA检测巨噬细胞IL-6、肿瘤坏死因子α(TNF-α)、诱导型一氧化氮合酶(i NOS)、CC趋化因子配体2(CCL2)、CD86、精氨酸酶1(Arg1)、甘露糖受体/CD206(MR/CD206)、IL-10、炎症区分子1(found in inflammatory zone 1,FIZZ1)、几丁质酶3样分子3(chitinase 3-like 3,即Ym-1)的变化。结果 ADSC使M1型巨噬细胞分泌的IL-6、TNF-α、i NOS、CCL2、CD86明显减少,Arg1、CD206、IL-10明显增加,且上清液中IL-6和TNF-α含量明显减少,CD206明显增加;使M2型巨噬细胞分泌的IL-6、TNF-α、i NOS、CD86明显减少,Arg1、CD206、FIZZ-1、Ym-1、IL-10明显增加,且上清液中IL-6和TNF-α含量明显减少,CD206明显增加。结论 ADSC抑制M1型巨噬细胞的特异性基因的表达,促进M2型巨噬细胞特异性基因的表达,并使M1型巨噬细胞向M2型巨噬细胞转化。Objective To investigate the effects of adipose-derived stem cells（ ADSCs） on M1/M2 macrophages and whether ADSCs are able to promote the polarization from M1 macrophages to M2 macrophages. Methods M1 macrophages were induced from J774. 1 macrophages by 24-hour stimulation of lipopolysaccharide（ LPS） and interferon γ（ IFN-γ）,and M2 macrophages were induced from J774. 1 macrophages by interleukin 4（ IL-4） for another 24 hours. Then M1 / M2 macrophages were separately cultured in the presence of ADSCs for 24 hours. The M1 / M2 macrophages and their corresponding supernatants were collected for further analysis. The expressions of IL-6,tumor necrosis factor α（ TNF-α）,inducible nitric oxide synthase（ i NOS）,CC chemokine ligand 2（ CCL2）,CD86,arginase 1（ Arg1）,mannose receptors / CD206（ MR /CD206）,IL-10,found in inflammatory zone 1（ FIZZ1）,chitinase 3-like 3（ Ym-1） were detected by real-time PCR and ELISA. Results ADSCs significantly decreased the levels of IL-6,TNF-α,i NOS,CCL2 and CD86,and increased the levels of Arg1,CD206 and IL-10 in M1 macrophages. In the supernatant of M1 macrophages,the expressions of IL-6 and TNF-αwere reduced,while those of CD206 were enhanced. In M2 macrophages,ADSCs resulted in down-regulation of IL-6,TNF-α,i NOS,CD86 and up-regulation of Arg1,CD206,FIZZ-1,Ym-1 and IL-10. In the supernatant of M2 macrophages,the expression levels of IL-6 and TNF-α were down-regulated and those of CD206 were up-regulated. Conclusion ADSCs can inhibit the gene expression of M1 macrophages and promote the gene expression of M2 macrophages,as well as mediate the polarization from M1 macrophages to M2 macrophages.

关 键 词：脂肪间充质干细胞 巨噬细胞极化 M1/M2型巨噬细胞 共培养 

分 类 号：R392.12[医药卫生—免疫学] R392.11[医药卫生—基础医学]