Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages

PLoS One. 2014 Dec 8;9(12):e113974. doi: 10.1371/journal.pone.0113974. eCollection 2014.

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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cattle
  • Cell Line
  • Cytokines / biosynthesis
  • Gene Knockdown Techniques
  • Humans
  • Inflammation Mediators / metabolism
  • Interferon Type I / pharmacology*
  • Interleukin-1beta / metabolism*
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Phagocytosis / genetics
  • Phagocytosis / immunology
  • Protein Multimerization
  • Reactive Oxygen Species / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, Scavenger / genetics
  • Receptors, Scavenger / metabolism
  • Silicon Dioxide / chemistry

Substances

  • Actins
  • Cytokines
  • Inflammation Mediators
  • Interferon Type I
  • Interleukin-1beta
  • MARCO protein, human
  • Reactive Oxygen Species
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Silicon Dioxide

Grants and funding

This study was performed by the grants from the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for Next Generation World-Leading Researchers (NEXT Program),” initiated by the Council for Science and Technology Policy (CSTP) (MT), MEXT-supported program for the Strategic Foundation at Private Universities (MT), Grant-in-Aid for Young Scientists (B) (KS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.