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Abstrakt

The main purpose of the study was to determine the safety of oclacitinib (OCL), a Janus kinase inhibitor, with respect of its effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. The mice were treated orally with OCL at a dose of 2.7 mg/kg for 14 days and peripheral blood, head and neck lymph nodes (HNLNs), mediastinal lymph nodes (MLNs) and spleen were collected. The study found that OCL induced depletion of CD4 + T cells in the HNLNs and MLNs, while it did not affect the absolute count of CD8 + T cells in these tissues. Also OCL caused a loss of B cells in the HNLNs, although not in the MLNs. Moreover, OCL depleted B cells in the peripheral blood, but did not affect the absolute count of CD4 + and CD8 + T cells. Thus, it can be concluded that OCL may induce a depletive effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. This effect should be seen as an unfavorable one, especially in patients with infections. Therefore, a clinical implication is that in such patients, the benefit/risk ratio should be thoroughly considered by clinicians. Moreover, OCL reduced the absolute count of eosinophils, basophils, neutrophils and monocytes. However, it is uncertain whether this effect should be considered to be of clinical importance because the levels of these cells were within the physiological range. It is possible that the depletive effect of OCL toward T and B cells, as well as eosinophils and basophils may contribute to the beneficial effects of the drug in the treatment of skin allergic diseases.
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Bibliografia

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Autorzy i Afiliacje

A. Jasiecka-Mikołajczyk
1
T. Maślanka
1

  1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-718 Olsztyn, Poland
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Abstrakt

The outbreak and prevalence of tembusu virus (TMUV) endanger the breeding industry of waterfowls. However, little is known about the molecular mechanism underlying TMUV infection. It was reported that heat shock protein 70 (HSP70) was a positive regulator of the infection of TMUV. In order to study the interactions between HSP70 and host immune response to TMUV infection, TMUV-infected cells with or without HSP70 inhibitor were harvested and subjected to deep sequencing to identify genes differentially expressed. We found 43 differentially expressed genes (DEGs) in HSP70 inhibitor-treated and mock-treated TMUV-infected DF-1 cells. Of these DEGs, 39 genes were down-regulated significantly. Gene Ontology analysis suggested that the DEGs were mainly involved in biological process, cellular component and molecular function. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs mainly related to the activation of innate immune response, including RIG-I-like receptor, toll-like receptor and NF-κB signaling pathway. Also, 12 down-regulated immune-related DEGs were selected for confirmation by reverse transcription quantitative real-time PCR verification, all these genes showed consistent expression between the result of reverse transcription quantitative real-time PCR and transcriptomic sequencing. These results revealed the important role of HSP70 in facilitating the innate immune response induced by TMUV infection. This is first to access the role of HSP70 in host response to TMUV infection, which provides a basis for further study of the pathogenesis of TMUV and contributes to the elucidation of TMUV-host interactions.
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Bibliografia


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Autorzy i Afiliacje

D. Zhao
1 2 3 4
K. Han
1 4
L. Zhang
1 4
X. Huang
1 4
Q. Liu.
1 4
J. Yang
1 4
Y. Liu
1 4
Y. Li
1 4
F. Wu
1 4

  1. Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, No. 50 Zhongling Street, Nanjing City, Jiangsu Province, 210014, PR China
  2. College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Tongwei Road, Nanjing City, Jiangsu Province 210095, PR China
  3. Institute of life sciences, Jiangsu University, No. 301 Xuefu Road, Zhenjiang, Jiangsu Province, 212013, PR China
  4. Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing City, Jiangsu Province, 210014, PR China

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