Department of Immunology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Torun, Poland.
Department of Regenerative Medicine Cell and Tissue Bank, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Torun, Poland.
Int J Mol Sci. 2023 Oct 27;24(21):15660. doi: 10.3390/ijms242115660.
gastritis is strongly associated with the upregulation of the expression of several matrix metalloproteinases (MMPs) in the gastric mucosa. However, the role of MMP-2 and MMP-9, and their inhibitors (tissue inhibitors of metalloproteinases -TIMPs) produced by immune cells in infected children have not been clearly defined. Moreover, the effects of eradication therapy on MMPs and TIMPs production has not been evaluated. A total of 84 children were studied: 24-with newly diagnosed gastritis, 25-after eradication therapy (17 of them after successful therapy), 24-with -negative gastritis, and 11-controls. Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 by ELISA; MMPs and TIMPs expression in lymphocytes; neutrophils and monocytes in peripheral blood by multiparameter flow cytometry; and mucosal mRNA expression levels of MMPs and TIMP-1 in gastric biopsies by RT-PCR were evaluated. Children with -related gastritis showed the following: (1) increased MMP-2 and TIMP-2 plasma levels, (2) increased intracellular expression of MMP-2 in the circulating lymphocytes and neutrophils, (3) low frequencies of circulating TIMP-1+ and TIMP-2+ leukocytes, and (4) high expression of mRNA for MMP-9 along with low expression of mRNA for MMP-2 in the gastric mucosa. Unsuccessful eradication was associated with the following: (1) high plasma levels of MMP-9 and TIMP-1, (2) increased pool of TIMP-1+ lymphocytes as well as high expression of MMP-9 in circulating lymphocytes, and (3) high expression of mRNA for MMP-9 in the gastric mucosa. Our data suggest that MMPs are important contributors to stomach remodelling in children with -related gastritis. Unsuccessful eradication is associated with increased MMP-9 in plasma, circulating lymphocytes, and gastric mucosa.
胃炎与胃黏膜中几种基质金属蛋白酶(MMPs)的表达上调密切相关。然而,免疫细胞产生的 MMP-2 和 MMP-9 及其抑制剂(金属蛋白酶组织抑制剂-TIMPs)的作用在感染儿童中尚未明确界定。此外,尚未评估根除疗法对 MMPs 和 TIMPs 产生的影响。共研究了 84 名儿童:24 名新诊断为胃炎,25 名接受根除治疗(其中 17 名治疗成功),24 名阴性胃炎,11 名对照。通过 ELISA 检测 MMP-2、MMP-9、TIMP-1 和 TIMP-2 的血浆水平;通过多参数流式细胞术检测淋巴细胞、外周血中性粒细胞和单核细胞中的 MMPs 和 TIMPs 表达;通过 RT-PCR 检测胃活检组织中 MMPs 和 TIMP-1 的黏膜 mRNA 表达水平。与幽门螺杆菌相关的胃炎患儿表现为:(1)血浆 MMP-2 和 TIMP-2 水平升高,(2)循环淋巴细胞和中性粒细胞内 MMP-2 表达增加,(3)循环 TIMP-1+和 TIMP-2+白细胞频率低,(4)胃黏膜中 MMP-9 的 mRNA 表达水平高,而 MMP-2 的 mRNA 表达水平低。根除治疗失败与以下因素相关:(1)血浆 MMP-9 和 TIMP-1 水平高,(2)循环淋巴细胞中 TIMP-1+淋巴细胞池增加以及循环淋巴细胞中 MMP-9 表达增加,(3)胃黏膜中 MMP-9 的 mRNA 表达水平高。我们的数据表明,MMPs 是儿童幽门螺杆菌相关胃炎胃重塑的重要贡献者。根除治疗失败与血浆、循环淋巴细胞和胃黏膜中 MMP-9 增加有关。