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Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway

Porcine circovirus type 2 (PCV2) is one of the major threats to pig farms worldwide. Although PCV2 has been identified to promote IL-10 production, the detailed regulatory roles of PCV2 Rep for IL-10 production remain unclear. Herein, we first found that PCV2 Rep, rather than PCV1 Rep, enhanced IL-1...

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Autores principales: Wu, Xingchen, Wang, Xiaoya, Shi, Tengfei, Luo, Le, Qiao, Dan, Wang, Zhenyu, Han, Cong, Du, Qian, Tong, Dewen, Huang, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950681/
https://www.ncbi.nlm.nih.gov/pubmed/31835539
http://dx.doi.org/10.3390/v11121141
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author Wu, Xingchen
Wang, Xiaoya
Shi, Tengfei
Luo, Le
Qiao, Dan
Wang, Zhenyu
Han, Cong
Du, Qian
Tong, Dewen
Huang, Yong
author_facet Wu, Xingchen
Wang, Xiaoya
Shi, Tengfei
Luo, Le
Qiao, Dan
Wang, Zhenyu
Han, Cong
Du, Qian
Tong, Dewen
Huang, Yong
author_sort Wu, Xingchen
collection PubMed
description Porcine circovirus type 2 (PCV2) is one of the major threats to pig farms worldwide. Although PCV2 has been identified to promote IL-10 production, the detailed regulatory roles of PCV2 Rep for IL-10 production remain unclear. Herein, we first found that PCV2 Rep, rather than PCV1 Rep, enhanced IL-10 expression at the later phase of PCV2 infection in porcine alveolar macrophages (PAMs). Furthermore, we found that PCV2 Rep directly activated the p38-MAPK pathway to promote transcription factors NF-κB p50 and Sp1 binding to the il10 promoter, but PCV1 Rep did not. During PCV2 infection, however, PCV2 Rep promoted the binding activities of NF-κB p50 and Sp1 with the il10 promoter only at the later phase of PCV2 infection, since Rep proteins only expressed at the later phase of the infection. Moreover, silence of the thymine DNA glycosylase (TDG), a Rep-binding protein, significantly reduced the binding activities of NF-κB p50 and Sp1 with il10 promoter, resulting in the reduction of IL-10 production in PCV2-inoculated PAMs at the later phase of infection. Taken together, our results demonstrate that Rep proteins enhance IL-10 production during PCV2 infection of PAMs via activation of p38-MAPK pathways, in which host TDG is a critical mediator.
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spelling pubmed-69506812020-01-16 Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway Wu, Xingchen Wang, Xiaoya Shi, Tengfei Luo, Le Qiao, Dan Wang, Zhenyu Han, Cong Du, Qian Tong, Dewen Huang, Yong Viruses Article Porcine circovirus type 2 (PCV2) is one of the major threats to pig farms worldwide. Although PCV2 has been identified to promote IL-10 production, the detailed regulatory roles of PCV2 Rep for IL-10 production remain unclear. Herein, we first found that PCV2 Rep, rather than PCV1 Rep, enhanced IL-10 expression at the later phase of PCV2 infection in porcine alveolar macrophages (PAMs). Furthermore, we found that PCV2 Rep directly activated the p38-MAPK pathway to promote transcription factors NF-κB p50 and Sp1 binding to the il10 promoter, but PCV1 Rep did not. During PCV2 infection, however, PCV2 Rep promoted the binding activities of NF-κB p50 and Sp1 with the il10 promoter only at the later phase of PCV2 infection, since Rep proteins only expressed at the later phase of the infection. Moreover, silence of the thymine DNA glycosylase (TDG), a Rep-binding protein, significantly reduced the binding activities of NF-κB p50 and Sp1 with il10 promoter, resulting in the reduction of IL-10 production in PCV2-inoculated PAMs at the later phase of infection. Taken together, our results demonstrate that Rep proteins enhance IL-10 production during PCV2 infection of PAMs via activation of p38-MAPK pathways, in which host TDG is a critical mediator. MDPI 2019-12-10 /pmc/articles/PMC6950681/ /pubmed/31835539 http://dx.doi.org/10.3390/v11121141 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Xingchen
Wang, Xiaoya
Shi, Tengfei
Luo, Le
Qiao, Dan
Wang, Zhenyu
Han, Cong
Du, Qian
Tong, Dewen
Huang, Yong
Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway
title Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway
title_full Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway
title_fullStr Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway
title_full_unstemmed Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway
title_short Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway
title_sort porcine circovirus type 2 rep enhances il-10 production in macrophages via activation of p38-mapk pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950681/
https://www.ncbi.nlm.nih.gov/pubmed/31835539
http://dx.doi.org/10.3390/v11121141
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