Negative Regulators of Inflammation Response to the Dynamic Expression of Cytokines in DF-1 and MDCK Cells Infected by Avian Influenza Viruses.

Bingqian Zhao,Baojian Li,Weixin Jia,Zhangyong Ning,Huizi Li,Wenxia Zhong,Suilan Cao

doi:10.1007/s10753-021-01568-y

Bingqian Zhao, Baojian Li + Show 5 more

Open Access

https://doi.org/10.1007/s10753-021-01568-y

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Abstract

The H5N1 and H9N2 avian influenza viruses (AIVs) seriously endanger the poultry industry and threaten human health. Characteristic inflammatory responses caused by H5N1 and H9N2 AIVs in birds and mammals result in unique clinical manifestations. The role of anti-inflammatory regulators, PTX3, Del-1, and GDF-15, in H5N1 and H9N2-AIV-mediated inflammation in birds and mammals has not yet been verified. Here, the expression of PTX3, Del-1, and GDF-15 in DF-1 and MDCK cells infected with H5N1 and H9N2 AIVs and their effect on inflammatory cytokines were analyzed. Infection with both AIVs increased PTX3, Del-1, and GDF-15 expression in DF-1 and MDCK cells. Infection with H9N2 or H5N1 AIV in DF-1 and MDCK cells with overexpression of all three factors, either alone or in combination, inhibited the expression of tested inflammatory cytokines. Furthermore, co-expression of PTX3, Del-1, and GDF-15 enhanced the inhibition, irrespective of the cell line. The findings from this study offer insight into the pathogenic differences between H5N1 and H9N2 AIVs in varied hosts. Moreover, our findings can be used to help screen for host-specific anti-inflammatory agents.

Highlights

Avian influenza virus (AIV), a type A influenza virus, is a threat to both the poultry industry and human health [1]
Expression of inflammatory cytokines in DF-1 and MDCK cells infected by H9N2 and H5N1 AIVs mRNA transcripts for inflammatory cytokines including IL-1β, IL-6 and TNF-α increased significantly in DF-1 and MDCK cells infected by H5N1 and H9N2 AIVs
In DF-1 cells, IL-1β, IL-6 and TNF-α increased significantly from 6 h after infection with both AIVs (p < 0.01), but greater expression levels were observed in response to H5N1 than H9N2 infection (Fig. 1A-C)

Summary

Introduction

Avian influenza virus (AIV), a type A influenza virus, is a threat to both the poultry industry and human health [1]. Based on their pathogenicity in chickens, AIVs can be divided into two groups––highly pathogenic avian influenza viruses (HPAIVs) and low pathogenic avian influenza viruses (LPAIVs) [2]. H9N2 AIV usually results in a mild host response, while H5N1 AIV causes respiratory distress syndrome and can even result in death [5, 6]. These clinical differences reflect the distinctive inflammatory responses caused by different AIV subtypes

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