Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages.
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 in...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4259327?pdf=render |
| _version_ | 1818252522886791168 |
|---|---|
| author | Kyoko Hara Koumei Shirasuna Fumitake Usui Tadayoshi Karasawa Yoshiko Mizushina Hiroaki Kimura Akira Kawashima Akihide Ohkuchi Shuichi Matsuyama Koji Kimura Masafumi Takahashi |
| author_facet | Kyoko Hara Koumei Shirasuna Fumitake Usui Tadayoshi Karasawa Yoshiko Mizushina Hiroaki Kimura Akira Kawashima Akihide Ohkuchi Shuichi Matsuyama Koji Kimura Masafumi Takahashi |
| author_sort | Kyoko Hara |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T16:25:31Z |
| format | Article |
| id | doaj.art-89a5a104d5cf4d208a890d87b3500d0d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T16:25:31Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-89a5a104d5cf4d208a890d87b3500d0d2022-12-22T00:18:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11397410.1371/journal.pone.0113974Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages.Kyoko HaraKoumei ShirasunaFumitake UsuiTadayoshi KarasawaYoshiko MizushinaHiroaki KimuraAkira KawashimaAkihide OhkuchiShuichi MatsuyamaKoji KimuraMasafumi TakahashiBACKGROUND: 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.http://europepmc.org/articles/PMC4259327?pdf=render |
| spellingShingle | Kyoko Hara Koumei Shirasuna Fumitake Usui Tadayoshi Karasawa Yoshiko Mizushina Hiroaki Kimura Akira Kawashima Akihide Ohkuchi Shuichi Matsuyama Koji Kimura Masafumi Takahashi Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. PLoS ONE |
| title | Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. |
| title_full | Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. |
| title_fullStr | Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. |
| title_full_unstemmed | Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. |
| title_short | Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. |
| title_sort | interferon tau attenuates uptake of nanoparticles and secretion of interleukin 1β in macrophages |
| url | http://europepmc.org/articles/PMC4259327?pdf=render |
| work_keys_str_mv | AT kyokohara interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT koumeishirasuna interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT fumitakeusui interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT tadayoshikarasawa interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT yoshikomizushina interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT hiroakikimura interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT akirakawashima interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT akihideohkuchi interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT shuichimatsuyama interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT kojikimura interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages AT masafumitakahashi interferontauattenuatesuptakeofnanoparticlesandsecretionofinterleukin1binmacrophages |