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先天性唇腭裂患儿唇部组织中细胞因子的定量分析

Quantification of Cytokines in Lip Tissue from Infants Affected by Congenital Cleft Lip and Palate.

作者信息

Pilmane Māra, Jain Nityanand, Jain Shivani, Akota Ilze, Kroiča Juta

机构信息

Department of Morphology, Institute of Anatomy and Anthropology, Riga Stradiņš University, LV-1007 Riga, Latvia.

Department of Oral and Maxillofacial Surgery, Genesis Institute of Dental Sciences & Research, Ferozepur, Punjab 152002, India.

出版信息

Children (Basel). 2021 Feb 12;8(2):140. doi: 10.3390/children8020140.

Abstract

Cleft lip and palate are amongst the most common congenital malformations worldwide presenting with variable manifestations. Previous research has been primarily focused on the genetical aspects of its complex and multifactorial etiology. In the present study, we investigated the role of cytokines as mediators of epithelial-mesenchymal crosstalk and local site inflammation in cleft affected infants. Lip material was obtained from 12 children aged before primary dentition who suffered from orofacial clefting. The quantification of 12 cytokines (Interleukin-2,4,5,6,10,12,13,17A, Tumor Necrosis Factor-α, Interferon-γ, Transforming Growth Factor beta-1 and Granulocyte-Colony Stimulating Factor) was done using ELISA. Nonparametric Spearman Rho was used to ascertain the correlation between the expression levels of different cytokines. A significantly strong positive correlation was found between IL-2 and IFN-γ coupled with an IL4/IFN-γ ratio favoring IFN-γ. These findings indicate a shift towards the preferential activation of the Th1 differentiation pathway. Further, a pathological reduction in TGFβ-1 levels was noted, which may contribute to mucosal damage. IL-6 was more highly correlated to IFN-γ and IL-12 indicating its potential proinflammatory role in cleft affected tissues. This preferential activation of Th1 cell differentiation and consistent expression of IL-2,6,13 and TNF-α in cleft patients may indicate certain underlying mechanisms for inflammation mediation at the site of clefting.

摘要

唇腭裂是全球最常见的先天性畸形之一,表现形式多样。以往的研究主要集中在其复杂的多因素病因的遗传学方面。在本研究中,我们调查了细胞因子作为上皮-间充质相互作用和唇腭裂患儿局部炎症介质的作用。从12名乳牙萌出前患有口腔颌面部裂的儿童获取唇部组织样本。使用酶联免疫吸附测定法(ELISA)对12种细胞因子(白细胞介素-2、4、5、6、10、12、13、17A、肿瘤坏死因子-α、干扰素-γ、转化生长因子β-1和粒细胞集落刺激因子)进行定量分析。采用非参数Spearman Rho检验确定不同细胞因子表达水平之间的相关性。结果发现白细胞介素-2和干扰素-γ之间存在显著的强正相关,且白细胞介素-4/干扰素-γ比值有利于干扰素-γ。这些发现表明向Th1分化途径的优先激活转变。此外,还注意到转化生长因子β-1水平病理性降低,这可能导致黏膜损伤。白细胞介素-6与干扰素-γ和白细胞介素-12的相关性更高,表明其在唇腭裂受累组织中可能具有促炎作用。唇腭裂患者中Th1细胞分化的这种优先激活以及白细胞介素-2、6、13和肿瘤坏死因子-α的持续表达可能表明在腭裂部位炎症介导的某些潜在机制。

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