Kono Y, Miyoshi S, Fujita T
Pharmazie. 2016 Nov 2;71(11):619-624. doi: 10.1691/ph.2016.6688.
Macrophages have been assumed to have a crucial role in the development of inflammatory bowel disease (IBD). However, involvement of intestinal macrophages in IBD onset and functional alterations of macrophages during IBD development has not been clarified. We investigated the effect of exposure of compounds used in the induction of colitis in mice on the immune responses of peritoneal macrophages in mice. 2,4,6- trinitrobenzenesulfonic acid and oxazolone did not affect the production of interleukin (IL)-10 and IL-12 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages from BALB/c mice. A significant increase in IL-10 secretion and decrease in IL-12 production from LPS-stimulated macrophages were observed upon exposure to dextran sodium sulfate (DSS). TNF-α production was enhanced significantly by exposure to DSS and LPS. The level of nitric-oxide production from macrophages was increased slightly by exposure to DSS and LPS. Expression of sphingosine kinase-1 and LIGHT (both of which are specific biomarkers of M2b macrophages) was observed in macrophages upon DSS exposure. Alteration of cytokine production in macrophages was observed upon DSS exposure in the absence of LPS stimulation. Peritoneal macrophages from C57BL/6 mice showed similar responses to peritoneal macrophages from BALB/c mice against DSS. These results suggest that DSS directs the immune response of macrophages towards the M2b phenotype.
巨噬细胞被认为在炎症性肠病(IBD)的发展中起关键作用。然而,肠道巨噬细胞在IBD发病中的作用以及IBD发展过程中巨噬细胞的功能改变尚未明确。我们研究了在小鼠中用于诱导结肠炎的化合物暴露对小鼠腹膜巨噬细胞免疫反应的影响。2,4,6-三硝基苯磺酸和恶唑酮不影响来自BALB/c小鼠的脂多糖(LPS)刺激的腹膜巨噬细胞产生白细胞介素(IL)-10和IL-12。暴露于葡聚糖硫酸钠(DSS)后,观察到LPS刺激的巨噬细胞中IL-10分泌显著增加,IL-12产生减少。暴露于DSS和LPS可显著增强肿瘤坏死因子-α(TNF-α)的产生。暴露于DSS和LPS后,巨噬细胞中一氧化氮的产生水平略有增加。暴露于DSS后,在巨噬细胞中观察到鞘氨醇激酶-1和LIGHT(两者均为M2b巨噬细胞的特异性生物标志物)的表达。在没有LPS刺激的情况下,暴露于DSS后观察到巨噬细胞中细胞因子产生的改变。来自C57BL/6小鼠的腹膜巨噬细胞对来自BALB/c小鼠的腹膜巨噬细胞对DSS的反应相似。这些结果表明,DSS将巨噬细胞的免疫反应导向M2b表型。