Interferon-Tau Attenuates Uptake of Nanoparticles and Secretion of Interleukin-1[beta] in Macrophages

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[beta], we examined the effects of ruminant IFNT on NLRP3 inflammasome-mediated IL-1[beta] secretion in human THP-1 macrophages. IFNT dose-dependently inhibited IL-1[beta] 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[beta] and mature IL-1[beta]. In addition, real-time RT-PCR analysis showed that IFNT suppressed IL-1[beta] 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[beta] secretion was restored by anti-IL-10 neutralizing antibody. Ruminant IFNT inhibits NLRP3 inflammasome-driven IL-1[beta] 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[beta] induction. It may be a therapeutic alternative to IFNA and IFNB.