Induction of interleukin-10 is dependent on p38 mitogen-activated protein kinase pathway in macrophages infected with porcine reproductive and respiratory syndrome virus
- Equal contributors
1 State Key Laboratories of Agrobiotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, 100193, China
2 Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, 100193, China
3 Present address: Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
4 Beijing Entry-exit inspection and quarantine bureau, No.6 Tian shui yuan road, Beijing, 100026, China
Virology Journal 2012, 9:165 doi:10.1186/1743-422X-9-165Published: 21 August 2012
Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure and respiratory illness in pigs and usually establishes a persistent infection. Previous studies suggested that interleukin-10 (IL-10) could play a critical role in PRRSV-induced immunosuppression. However, the ability of PRRSV to induce IL-10 in infected cells is controversial. In this study, we further investigated this issue using PRRSV strain CH-1a, which is the first North American genotype strain isolated in China.
PRRSV strain CH-1a could significantly up-regulate IL-10 production both at mRNA and protein levels in porcine alveolar macrophages (PAMs), bone marrow-derived macrophages (BMDMs), and monocyte-derived macrophages (MDMs). However, up-regulation of IL-10 by PRRSV was retarded by specific inhibitors of p38 mitogen-activated protein kinase (MAPK) (SB203580) and NF-κB (BAY11-7082). Additionally, p38 MAPK and NF-κB pathways but not ERK1/2 MAPK were actually activated in PRRSV-infected BMDMs as demonstrated by western blot analysis, suggesting that p38 MAPK and NF-κB pathways are involved in the induction of IL-10 by PRRSV infection. Transfection of PAMs and PAM cell line 3D4/21 (CRL-2843) with viral structural genes showed that glycoprotein5 (GP5) could significantly up-regulate IL-10 production, which was dependent on p38 MAPK and signal transducer and activator of transcription-3 (STAT3) activation. We also demonstrated that a full-length glycoprotein was essential for GP5 to induce IL-10 production.
PRRSV strain CH-1a could significantly up-regulate IL-10 production through p38 MAPK activation.