Dataset Information

Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1? 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)-1?, we examined the effects of ruminant IFNT on NLRP3 inflammasome-mediated IL-1? secretion in human THP-1 macrophages.

Methods and results

IFNT dose-dependently inhibited IL-1? 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-1? and mature IL-1?. In addition, real-time RT-PCR analysis showed that IFNT suppressed IL-1? 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-1? secretion was restored by anti-IL-10 neutralizing antibody.

Conclusions

Ruminant IFNT inhibits NLRP3 inflammasome-driven IL-1? 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-1? induction. It may be a therapeutic alternative to IFNA and IFNB.

SUBMITTER: Hara K

PROVIDER: S-EPMC4259327 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hara Kyoko K Shirasuna Koumei K Usui Fumitake F Karasawa Tadayoshi T Mizushina Yoshiko Y Kimura Hiroaki H Kawashima Akira A Ohkuchi Akihide A Matsuyama Shuichi S Kimura Koji K Takahashi Masafumi M

PloS one 20141208 12

<h4>Background</h4>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 sec ...[more]

PMID: 25486008

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