ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection
ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection
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ITIH4作为炎症生物标志物，主要在细菌血流感染时增加
DOI：
10.1016/j.cyto.2020.155377
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发表时间：
2021-02-01
期刊：
影响因子：
3.8
通讯作者：
Wang, Chengbin
中科院分区：
文献类型：
--
作者：
Ma, Yating;Li, Ruibing;Wang, Chengbin
血流感染通常伴随着多种炎症蛋白的改变。在我们之前的研究中，我们发现α -胰蛋白酶间抑制剂重链H4 （ITIH4）在感染组中比正常对照组高表达。然而，相关的验证和机制尚不清楚。采用ELISA法验证大肠杆菌感染小鼠模型和临床血清样品中白细胞介素-6 （IL-6）、肿瘤坏死因子- α (tnf - α)、白细胞介素-10 （IL-10）和ITIH4的浓度。采用细胞因子（IL-6、tnf - α、IL-10和脂多糖（LPS））刺激HepG2细胞模型，探讨哪些细胞因子影响ITIH4的表达。JAK/STAT抑制剂在IL-6和LPS刺激前处理。采用Westernblot和real-time PCR从蛋白和转录水平检测肝组织中ITIH4的表达。免疫组化法观察ITIH4在小鼠肝组织中的表达。在小鼠模型中，感染组的IL-6、tnf - α和IL-10均高于正常对照组。模型小鼠血清和肝组织中ITIH4含量从1 h升高至128 h，与正常对照组差异显著。此外，临床血清样品中细菌感染组的ITIH4明显高于真菌血症组、肺炎支原体（MP）组和发热组。此外，使用HepG2细胞系，我们证明了在IL-6和LPS的剂量和时间反应处理下，ITIH4在蛋白质和mRNA水平上都上调。此外，用JAK/STAT抑制剂处理IL-6或LPS介导的ITIH4表达可显著降低蛋白或mRNA水平。tnf - α或IL-10刺激后未见变化。ITIH4可能是一个关键的炎症生物标志物，与BSI的发展有关，特别是与细菌性血流感染有关。本研究有望为BSI的潜在功能机制提供一些见解。
Bloodstream infection (BSI) is usually accompanied with the changes of varieties of inflammation proteins. In our previous study, we identified that inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) was highly expressed in the infection arms than the normal control arm. However, the correlated verification and mechanism remain obscure. Escherichia coli infected mice model and clinical serum samples were used to validate the concentration of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), as well as ITIH4, in ELISA method. Cytokines (IL-6, TNF-alpha, IL-10 and lipopolysaccharide (LPS)) were used to stimulate the HepG2 cell model to explore which cytokines influence the expression of ITIH4. JAK/STAT inhibitor was treated before IL-6 and LPS stimulation. Westernblot, as well as real-time PCR were performed to detect the expression of ITIH4 in liver tissue from protein and transcription levels. Immunohistochemistry analysis was used to observe the expression of ITIH4 in mice liver tissue. In mice model, IL-6, TNF-alpha, as well as IL-10 increased in the infection arms than the normal control arm. ITIH4 in serum and liver tissue of mice model increased from 1 h to 128 h, which were remarkably different from that of the normal control arm. Besides, ITIH4 increased in the bacterial infection arm greatly than the fungemia arm, mycoplasma pneumoniae (MP) arm and febrile arm in clinical serum samples. Furthermore, using the HepG2 cell line, we demonstrated that ITIH4 was up-regulated at both protein and mRNA levels upon doseand timeresponse treatments with IL-6, as well as LPS. Moreover, IL-6 or LPS mediated induction of ITIH4 expression could be significantly decreased by treatment with an JAK/STAT inhibitor in protein or mRNA level. No changes were observed after TNF-alpha or IL-10 stimulation. ITIH4 might be a critical inflammatory biomarker which correlated with the development of BSI, especially with bacterial bloodstream infection. It is expected that this study would provide some insights into potential functional mechanisms underlying BSI.