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Virol Sin. 2019 Dec;34(6):648-661. doi: 10.1007/s12250-019-00145-w. Epub 2019 Jul 8.

The Establishment and Validation of the Human U937 Cell Line as a Cellular Model to Screen Immunomodulatory Agents Regulating Cytokine Release Induced by Influenza Virus Infection.

Liu G1,2, Chen S1,2, Hu A1,2, Zhang L1,2, Sun W1,2, Chen J1, Tang W1, Zhang H1, Liu C1, Ke C3, Chen X4,5.

Author information

1
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
2
University of Chinese Academy of Sciences, Beijing, 100049, China.
3
Wuhan Virolead Biopharmaceutical Company, Wuhan, 430075, China.
4
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. chenxl@wh.iov.cn.
5
University of Chinese Academy of Sciences, Beijing, 100049, China. chenxl@wh.iov.cn.

Abstract

Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines, which is also referred to as "cytokine storms". Several studies have shown that cytokine storms are directly associated with influenza-induced fatal acute lung injury and acute respiratory distress syndrome. Due to the narrow administration window, current antiviral therapies are often inadequate. The efforts to use immunomodulatory agents alone or in combination with antiviral agents in the treatment of influenza in animal models have resulted in the achievement of protective effects accompanied with reduced cytokine production. Currently, there are no immunomodulatory drugs for influenza available for clinical use. Animal models, despite being ideal to study the anti-inflammatory responses to influenza virus infection, are very costly and time-consuming. Therefore, there is an urgent need to establish fast and economical screening methods using cell-based models to screen and develop novel immunomodulatory agents. In this study, we screened seven human cell lines and found that the human monocytic cell U937 supports the replication of different subtypes of influenza viruses as well as the production of the important pro-inflammatory cytokines and was selected to develop the cell-based model. The U937 cell model was validated by testing a panel of known antiviral and immunomodulatory agents and screening a drug library consisting of 1280 compounds comprised mostly of FDA-approved drugs. We demonstrated that the U937 cell model is robust and suitable for the high-throughput screening of immunomodulators and antivirals against influenza infection.

KEYWORDS:

CCL2; CXCL10; Immunomodulatory agent; Influenza; U937 cell

PMID:
31286365
PMCID:
PMC6889097
DOI:
10.1007/s12250-019-00145-w
[Indexed for MEDLINE]
Free PMC Article

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