title: Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages.
abstract: BACKGROUND
  Type I interferons (IFNs), including IFN-alpha (IFNA) and IFN-beta (IFNB), have anti-inflammatory properties and are used to treat patients with autoimmune and inflammatory disorders. However, little is known of the role of IFN-tau (IFNT), a type I IFN produced by ruminant animals for inflammation. Because IFNB has recently been shown to inhibit nucleotide-binding oligomerization domain-like receptor, pyrin domain-containing 3 (NLRP3) inflammasome activation and subsequent secretion of the potent inflammatory cytokine interleukin (IL)-1β, we examined the effects of ruminant IFNT on NLRP3 inflammasome-mediated IL-1β secretion in human THP-1 macrophages.
  
  
  RESULTS
  IFNT dose-dependently inhibited IL-1β secretion induced by nano-silica, a well-known activators of NLRP3 inflammasomes, in human macrophages primed with lipopolysaccharide (LPS, TLR4 agonist) and Pam3CSK4 (TLR1/2 agonist). IFNT also suppressed phagocytosis of nano-silica and reactive oxygen species (ROS) generation. Western blot analysis showed that IFNT inhibited both pro-IL-1β and mature IL-1β. In addition, real-time RT-PCR analysis showed that IFNT suppressed IL-1β mRNA expression induced by LPS and Pam3CSK4. Although nano-silica particles did not induce IL-10 secretion, IFNT induced IL-10 secretion in a dose-dependent manner. Furthermore, IFNT-suppressed IL-1β secretion was restored by anti-IL-10 neutralizing antibody.
  
  
  CONCLUSIONS
  Ruminant IFNT inhibits NLRP3 inflammasome-driven IL-1β secretion in human macrophages via multiple pathways, including the uptake of nano-silica particles, generation of ROS, and IL-10-mediated inhibition of pro-IL-1β induction. It may be a therapeutic alternative to IFNA and IFNB.
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hara
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan; Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa, Japan.
authors.forename: Koumei
authors.initials: K
authors.lastname: Shirasuna
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Usui
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Karasawa
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mizushina
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ohkuchi
authors.affiliation: Animal Feeding and Management Research Division, National Institute of Livestock and Grassland Science, Nasushiobara, Tochigi, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Matsuyama
authors.affiliation: Animal Feeding and Management Research Division, National Institute of Livestock and Grassland Science, Nasushiobara, Tochigi, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D055503:Protein Multimerization; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D000199:Actins; D016207:Cytokines; D018836:Inflammation Mediators; D007370:Interferon Type I; D053583:Interleukin-1beta; C490460:MARCO protein, human; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D012822:Silicon Dioxide