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人类活动期眼弓形虫病局部和全身的 IL-10、IL-17 和 TGF-β 的基因表达水平。

Local and systemic gene expression levels of IL-10, IL-17 and TGF-β in active ocular toxoplasmosis in humans.

机构信息

Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Cytokine. 2021 Oct;146:155643. doi: 10.1016/j.cyto.2021.155643. Epub 2021 Jul 28.

DOI:10.1016/j.cyto.2021.155643
PMID:34332275
Abstract

BACKGROUND

To compare mRNA expression of interleukin 10 (IL-10), interleukin 17 (IL-17) and Transforming Growth Factor-β (TGF-β) in aqueous humor (AH) and peripheral blood mononuclear cells (PBMCs) in human ocular toxoplasmosis (OT) and controls.

METHOD

RNA isolation, cDNA synthesis and real-time polymerase chain reaction were performed on AH sediments and PBMCs of 16 patients with active OT and 21 controls at the Khatam-al-Anbia Eye Hospital, Iran. For comparison, Mann Whitney U test was used at a discrimination level of p < 0.05. Pearson and Spearman rank correlation test were applied for correlation with clinical parameters.

RESULTS

The expression for IL-10 and IL-17 in the AH was 3.7- and 88.0-fold higher in OT than in controls (P = 0.04 and P = 0.03, respectively) whereas that of TGF-β was 7.7-fold lower (P < 0.001). The expression levels for these cytokines in PBMC followed a similar pattern (IL-10 13.8-fold down-regulated (P = 0.001), IL-17 with 1.9-fold insignificantly upregulated (p = 0.43), TGF-β 452.8-fold down-regulated (P = 0.002). Compared to PBMC, IL-10 coding mRNA was 1876-fold higher in the almost cell-free AH in OT (39.2-fold in controls), IL-17 coding mRNA was 9.4-fold higher (17.7-fold down-regulated in controls), and that coding for TGF-β 207-fold higher in OT (7x10-fold in controls). The expression for IL-10, IL-17 and TGF-β in AH thus followed an opposite pattern compared to that in PBMC.

CONCLUSION

OT induces a highly-specific local immunoregulatory process as evidenced by an intraocular up-regulation of IL-10 and down-regulation of TGF-β mRNA. This could indicate an attempt to prevent unnecessary tissue damage which is in line with a moderate local mRNA up-regulation for IL-17 which seems sufficient to control parasite proliferation. That this regulation is opposite to that in PBMC may be linked to intraocular immune deviation in the course of disease.

摘要

背景

比较人眼弓形体病(OT)患者和对照组房水(AH)和外周血单个核细胞(PBMC)中白细胞介素 10(IL-10)、白细胞介素 17(IL-17)和转化生长因子-β(TGF-β)的 mRNA 表达。

方法

在伊朗 Khatam-al-Anbia 眼科医院,对 16 例活动性 OT 患者和 21 例对照组的 AH 沉淀物和 PBMC 进行 RNA 分离、cDNA 合成和实时聚合酶链反应。为了进行比较,采用 Mann Whitney U 检验,差异水平为 p < 0.05。采用 Pearson 和 Spearman 秩相关检验与临床参数进行相关性分析。

结果

OT 患者的 AH 中 IL-10 和 IL-17 的表达分别比对照组高 3.7 倍和 88.0 倍(P=0.04 和 P=0.03),而 TGF-β 的表达则低 7.7 倍(P<0.001)。这些细胞因子在 PBMC 中的表达水平也呈现出类似的模式(IL-10 下调 13.8 倍(P=0.001),IL-17 上调 1.9 倍,但无统计学意义(p=0.43),TGF-β 下调 452.8 倍(P=0.002)。与 PBMC 相比,OT 患者的几乎无细胞 AH 中 IL-10 编码 mRNA 高 1876 倍(对照组中为 39.2 倍),IL-17 编码 mRNA 高 9.4 倍(对照组中为 17.7 倍下调),TGF-β 编码 mRNA 高 207 倍(对照组中为 7x10 倍)。因此,AH 中 IL-10、IL-17 和 TGF-β 的表达与 PBMC 中的表达相反。

结论

OT 诱导一种高度特异性的局部免疫调节过程,表现为眼内 IL-10 上调和 TGF-β mRNA 下调。这可能表明一种试图防止不必要的组织损伤的尝试,这与 IL-17 的局部 mRNA 适度上调一致,这似乎足以控制寄生虫增殖。这种调节与 PBMC 中的调节相反,可能与疾病过程中的眼内免疫偏离有关。

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