PMID- 22909062 OWN - NLM STAT- MEDLINE DCOM- 20130123 LR - 20211021 IS - 1743-422X (Electronic) IS - 1743-422X (Linking) VI - 9 DP - 2012 Aug 21 TI - Induction of interleukin-10 is dependent on p38 mitogen-activated protein kinase pathway in macrophages infected with porcine reproductive and respiratory syndrome virus. PG - 165 LID - 10.1186/1743-422X-9-165 [doi] AB - BACKGROUND: 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. RESULTS: 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-kappaB (BAY11-7082). Additionally, p38 MAPK and NF-kappaB 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-kappaB 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. CONCLUSIONS: PRRSV strain CH-1a could significantly up-regulate IL-10 production through p38 MAPK activation. FAU - Hou, Jun AU - Hou J AD - State Key Laboratories of Agrobiotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, 100193, China. FAU - Wang, Lianghai AU - Wang L FAU - Quan, Rong AU - Quan R FAU - Fu, Yi AU - Fu Y FAU - Zhang, Hexiao AU - Zhang H FAU - Feng, Wen-hai AU - Feng WH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120821 PL - England TA - Virol J JT - Virology journal JID - 101231645 RN - 130068-27-8 (Interleukin-10) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Blotting, Western MH - Cell Line MH - China MH - Gene Expression Profiling MH - Interleukin-10/*biosynthesis/immunology MH - Macrophages/*immunology/*virology MH - Porcine respiratory and reproductive syndrome virus/*immunology MH - Swine MH - p38 Mitogen-Activated Protein Kinases/immunology/*metabolism PMC - PMC3441385 EDAT- 2012/08/23 06:00 MHDA- 2013/01/24 06:00 PMCR- 2012/08/21 CRDT- 2012/08/23 06:00 PHST- 2012/01/26 00:00 [received] PHST- 2012/08/07 00:00 [accepted] PHST- 2012/08/23 06:00 [entrez] PHST- 2012/08/23 06:00 [pubmed] PHST- 2013/01/24 06:00 [medline] PHST- 2012/08/21 00:00 [pmc-release] AID - 1743-422X-9-165 [pii] AID - 10.1186/1743-422X-9-165 [doi] PST - epublish SO - Virol J. 2012 Aug 21;9:165. doi: 10.1186/1743-422X-9-165.