The influence of vitamin D on M1 and M2 macrophages in patients with Crohn's disease

The influence of vitamin D on M1 and M2 macrophages in patients with Crohn's disease
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DOI:
10.1177/1753425917721965
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发表时间:
2017-08-01
期刊:
影响因子:
3.2
通讯作者:
Seidman, Ernest G.
Seidman, Ernest G.
中科院分区:
生物学4区
文献类型:
--
作者:
Dionne, Serge;Duchatelier, Carl-Frederic;Seidman, Ernest G.

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巨噬细胞对细菌的清除能力不足在克罗恩病(CD)中起着重要作用。尚未研究CD中炎性M1和抗炎性M2的表型和功能。补充维生素D通过不清楚的机制降低CD的严重程度。我们研究了CD和对照组的巨噬细胞特征以及1,25维生素D(1,25 D)的影响。从CD患者和对照中分离PBMC。通过分别用GM-CSF和M-CSF培养单核细胞生成M1和M2。CD M1和M2对CCL 2和fMLP具有正常的吞噬和趋化作用。LPS诱导的TNF-α、IL-12 p40和IL-10的产生在组间相当。1,25 D的吞噬作用没有改变;迁移仅略微增加。M1产生更多的IL-12 p40和TNF-α; M2中IL-10更高。1,25 D显著降低M1和M2的IL-12 p40。1,25 D降低CD M1中的TNF-α; IL-10水平不受影响。M2表达F13 A1、PTGS 2、CD 163、CXCL 10、CD 14和MMP 2,而TGF-β、CCL 1和CYP 27 B1在M1中表达更高。CD和对照之间的标志物表达相似。M1和M2标记不受1,25 D的差异调节。CD巨噬细胞与对照相比在功能或表型上没有差异。1,25 D显著降低促炎性M1细胞因子,但不调节极化至抗炎性M2表型。
Defective bacterial clearance by macrophages plays an important role in Crohn's disease (CD). Phenotypes and functions of inflammatory M1 and anti-inflammatory M2 have not been studied in CD. Vitamin D supplementation reduces the severity of CD by unclear mechanisms. We studied macrophage characteristics in CD and controls and the effects of 1,25 vitamin D (1,25D). PBMC were isolated from CD patients and controls. M1 and M2 were generated by culturing of monocytes with GM-CSF and M-CSF, respectively. CD M1 and M2 showed normal phagocytosis and chemotaxis to CCL2 and fMLP. LPS-induced production of TNF-, IL-12p40 and IL-10 was comparable between groups. Phagocytosis was unaltered with 1,25D; migration only increased marginally. M1 produced more IL-12p40 and TNF-; IL-10 was greater in M2. 1,25D markedly decreased IL-12p40 by M1 and M2. 1,25D decreased TNF- in CD M1; IL-10 levels were unaffected. M2 express F13A1, PTGS2, CD163, CXCL10, CD14 and MMP2, whereas TGF-, CCL1 and CYP27B1 expression was higher in M1. Marker expression was similar between CD and controls. M1 and M2 markers were not differentially modulated by 1,25D. CD macrophages are not functionally or phenotypically different vs. controls. 1,25D markedly decreased pro-inflammatory M1 cytokines but did not modulate polarization to anti-inflammatory M2 phenotype.