title: Interleukin-1 receptor antagonist: an early immunomodulatory cytokine induced by porcine reproductive and respiratory syndrome virus.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) infection poorly induces pro-inflammatory cytokines (IL-1, IL-6 and TNF-α) and type I IFN production during the early phase of infection. Our microarray analysis indicated strong upregulation of the IL1RA gene in type 2 PRRSV -infected monocyte-derived dendritic cells. Interleukin-1 receptor antagonist (IL-1Ra) is an early inhibitory cytokine that suppresses pro-inflammatory cytokines and T-lymphocyte responses. To investigate the induction of IL-1Ra by PRRSV, monocyte-derived dendritic cells were cultured with type 2 PRRSV or other swine viruses. PRRSV increased both IL1RA gene expression and IL-1Ra protein production in the culture. The enhanced production of IL-1Ra was further confirmed in PRRSV-cultured PBMC and PRRSV-exposed pigs by flow cytometry. Myeloid cell population appeared to be the major IL-1Ra producer both in vitro and in vivo. In contrast to the type 2 PRRSV, the highly pathogenic (HP)- PRRSV did not upregulate IL1RA gene expression in vitro. To determine the kinetics of PRRSV-induced IL1RA gene expression in relation to other pro-inflammatory cytokine genes, PRRSV-negative pigs were vaccinated with a commercially available type 2 modified-live PRRS vaccine or intranasally inoculated with HP-PRRSV. In modified-live PRRS vaccine pigs, upregulation of IL1RA, but not IL1B and IFNA, gene expression was observed from 2 days post- vaccination. Consistent with the in vitro findings, upregulation of IL1RA gene expression was not observed in the HP-PRRSV-infected pigs throughout the experiment. This study identified IL-1Ra as an early immunomodulatory mediator that could be involved in the immunopathogenesis of PRRSV infections.
authors.affiliation: Interdisciplinary Program of Medical Microbiology, Graduate School, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Teerawut
authors.initials: T
authors.lastname: Nedumpun
authors.affiliation: Department of Medical Technology, Faculty of Science and Technology, Bansomdejchaopraya Rajabhat University, Bangkok, Thailand.
authors.forename: Piya
authors.initials: P
authors.lastname: Wongyanin
authors.affiliation: Graduate Program in Veterinary Pathobiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Chaitawat
authors.initials: C
authors.lastname: Sirisereewan
authors.affiliation: Department of Microbiology, RU in Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Patcharee
authors.initials: P
authors.lastname: Ritprajak
authors.affiliation: Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Tanapat
authors.initials: T
authors.lastname: Palaga
authors.affiliation: Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Bangkok, Thailand.|Department of Veterinary Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Roongroje
authors.initials: R
authors.lastname: Thanawongnuwech
authors.affiliation: Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.|Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Bangkok, Thailand.
authors.forename: Sanipa
authors.initials: S
authors.lastname: Suradhat
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000473:pathology; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013552:Swine; D015854:Up-Regulation
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1