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鉴定新型炎症细胞因子和角质形成细胞衍生趋化因子对创伤弧菌感染小鼠炎症反应的贡献。

Identification of Novel Inflammatory Cytokines and Contribution of Keratinocyte-Derived Chemokine to Inflammation in Response to Vibrio vulnificus Infection in Mice.

机构信息

Department of Laboratory Medicine, General Hospital of Ji'nan Military Region of PLA, Ji'nan, 250031, Shandong Province, People's Republic of China.

出版信息

Inflammation. 2015 Oct;38(5):1864-73. doi: 10.1007/s10753-015-0166-5.

Abstract

Currently, only tumor necrosis factor alpha (TNF-α) and interleukin family cytokines have been found to be elicited in Vibrio vulnificus (V. vulnificus)-infected animal models and humans. However, multiple other cytokines are also involved in the immune and inflammatory responses to foreign microorganism infection. Antibody array technology, unlike traditional enzyme-linked immunosorbent assay (ELISA), is able to detect multiple cytokines at one time. Therefore, in this study, we examined the proinflammatory cytokine profile in the serum and liver homogenate samples of bacterial-infected mice using antibody array technology. We identified nine novel cytokines in response to V. vulnificus infection in mice. We found that keratinocyte-derived chemokine (KC) was the most elevated cytokine and demonstrated that KC played a very important role in the V. vulnificus infection-elicited inflammatory response in mice, as evidenced by the fact that the blocking of KC by anti-KC antibody reduced hepatic injury in vivo and that KC induced by V. vulnificus infection in AML-12 cells chemoattracted neutrophils. Our findings implicate that KC may serve as a novel diagnostic biomarker and a possible therapeutic target for V. vulnificus infection.

摘要

目前,仅在创伤弧菌(Vibrio vulnificus,V. vulnificus)感染动物模型和人类中发现肿瘤坏死因子-α(tumor necrosis factor alpha,TNF-α)和白细胞介素家族细胞因子被引发。然而,其他多种细胞因子也参与了对外源微生物感染的免疫和炎症反应。与传统的酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)相比,抗体芯片技术能够一次检测多种细胞因子。因此,在这项研究中,我们使用抗体芯片技术检测了细菌感染小鼠的血清和肝匀浆样本中的促炎细胞因子谱。我们在小鼠感染创伤弧菌后鉴定出 9 种新的细胞因子。我们发现,角质细胞衍生趋化因子(keratinocyte-derived chemokine,KC)是上调最显著的细胞因子,并证明 KC 在创伤弧菌感染诱导的小鼠炎症反应中起着非常重要的作用,这一事实表明,通过抗 KC 抗体阻断 KC 可减少体内肝损伤,而创伤弧菌感染 AML-12 细胞诱导的 KC 可趋化中性粒细胞。我们的研究结果表明,KC 可能成为创伤弧菌感染的一种新的诊断生物标志物和可能的治疗靶点。

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