Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages.
Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages.
复制标题
DOI：
10.1371/journal.pone.0113974
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Takahashi M
中科院分区：
文献类型：
--
作者：
Hara K;Shirasuna K;Usui F;Karasawa T;Mizushina Y;Kimura H;Kawashima A;Ohkuchi A;Matsuyama S;Kimura K;Takahashi M
I型干扰素（ifn），包括ifn - α (IFNA)和ifn - β (IFNB)，具有抗炎特性，用于治疗自身免疫性和炎症性疾病患者。然而，人们对IFN-tau （IFNT）的作用知之甚少，IFNT是反刍动物产生的用于炎症的I型IFN。由于IFNB最近被证明可以抑制核苷酸结合寡聚化结构域样受体、pyrin结构域- 3 （NLRP3）炎性小体的激活和随后强效炎性细胞因子白细胞介素(IL)-1β的分泌，我们研究了反刍动物IFNT对NLRP3炎性小体介导的人THP-1巨噬细胞分泌IL-1β的影响。IFNT剂量依赖性地抑制由纳米二氧化硅诱导的IL-1β分泌，纳米二氧化硅是一种众所周知的NLRP3炎症小体的激活剂，在脂多糖（LPS， TLR4激动剂）和Pam3CSK4 （TLR1/2激动剂）引发的人巨噬细胞中。IFNT还抑制了纳米二氧化硅的吞噬作用和活性氧（ROS）的产生。Western blot分析显示，IFNT对IL-1β前体和成熟IL-1β均有抑制作用。实时RT-PCR分析显示，IFNT抑制LPS和Pam3CSK4诱导的IL-1β mRNA表达。虽然纳米二氧化硅颗粒不诱导IL-10分泌，但IFNT诱导IL-10分泌呈剂量依赖性。此外，抗il -10中和抗体可恢复ifnt抑制的IL-1β分泌。反刍动物IFNT通过多种途径抑制人巨噬细胞NLRP3炎症小体驱动的IL-1β分泌，包括纳米二氧化硅颗粒的摄取、ROS的产生和il -10介导的对IL-1β诱导的抑制。它可能是IFNA和IFNB的治疗选择。
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. 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. 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.
登录
查看更多内容
影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
DOI：
10.4161/jkst.23820
发表时间：
2013-01-01
期刊：
JAK-STAT
影响因子：
--
作者：
Rauch I;Müller M;Decker T
通讯作者：
Decker T
影响因子：
4.4
作者：
Soos, JM;Stüve, O;Zamvil, SS
通讯作者：
Zamvil, SS
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.8
作者：
Kanno, Sanae;Furuyama, Akiko;Hirano, Seishiro
通讯作者：
Hirano, Seishiro