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

Kyoko Hara, Koumei Shirasuna, Fumitake Usui, Tadayoshi Karasawa, Yoshiko Mizushina, Hiroaki Kimura, Akira Kawashima, Akihide Ohkuchi, Shuichi Matsuyama, Koji Kimura, Masafumi Takahashi

Research output: Contribution to journalArticle

18 Citations (Scopus)

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, IFNTsuppressed 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.

Original languageEnglish
Article numbere113974
JournalPloS one
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 8 2014
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Hara, K., Shirasuna, K., Usui, F., Karasawa, T., Mizushina, Y., Kimura, H., Kawashima, A., Ohkuchi, A., Matsuyama, S., Kimura, K., & Takahashi, M. (2014). Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. PloS one, 9(12), [e113974]. https://doi.org/10.1371/journal.pone.0113974