The Experts below are selected from a list of 117 Experts worldwide ranked by ideXlab platform
Hidenori Ichijo - One of the best experts on this subject based on the ideXlab platform.
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ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity
Nature Immunology, 2005Co-Authors: Atsushi Matsuzawa, Kaoru Saegusa, Takuya Noguchi, Chiharu Sadamitsu, Hideki Nishitoh, Shigenori Nagai, Shigeo Koyasu, Kunihiro Matsumoto, Kohsuke Takeda, Hidenori IchijoAbstract:Apoptosis signal–regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen-activated protein kinases. Here we used ASK1-deficient mice to show that ASK1 was selectively required for Lipopolysaccharide-Induced activation of p38 but not of Jnk or the transcription factor NF-κB. ASK1 was required for the induction of proinflammatory cytokines dependent on Toll-like receptor 4 (TLR4) but not TLR2 or other TLRs. Consistent with this, ASK1-deficient mice were resistant to Lipopolysaccharide-Induced Septic Shock. Lipopolysaccharide induced the production of intracellular reactive oxygen species, which was required for the formation of a complex of the adaptor molecule TRAF6 and ASK1 and subsequent activation of the ASK1-p38 pathway. Our data demonstrate that the reactive oxygen species–dependent TRAF6-ASK1-p38 axis is crucial for TLR4-mediated mammalian innate immunity.
Atsushi Matsuzawa - One of the best experts on this subject based on the ideXlab platform.
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ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity
Nature Immunology, 2005Co-Authors: Atsushi Matsuzawa, Kaoru Saegusa, Takuya Noguchi, Chiharu Sadamitsu, Hideki Nishitoh, Shigenori Nagai, Shigeo Koyasu, Kunihiro Matsumoto, Kohsuke Takeda, Hidenori IchijoAbstract:Apoptosis signal–regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen-activated protein kinases. Here we used ASK1-deficient mice to show that ASK1 was selectively required for Lipopolysaccharide-Induced activation of p38 but not of Jnk or the transcription factor NF-κB. ASK1 was required for the induction of proinflammatory cytokines dependent on Toll-like receptor 4 (TLR4) but not TLR2 or other TLRs. Consistent with this, ASK1-deficient mice were resistant to Lipopolysaccharide-Induced Septic Shock. Lipopolysaccharide induced the production of intracellular reactive oxygen species, which was required for the formation of a complex of the adaptor molecule TRAF6 and ASK1 and subsequent activation of the ASK1-p38 pathway. Our data demonstrate that the reactive oxygen species–dependent TRAF6-ASK1-p38 axis is crucial for TLR4-mediated mammalian innate immunity.
Xiaoyan Xu - One of the best experts on this subject based on the ideXlab platform.
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er localized hrd1 ubiquitinates and inactivates usp15 to promote tlr4 induced inflammation during bacterial infection
Nature microbiology, 2019Co-Authors: Yao Lu, Haishuang Chang, Ruiyue Zhong, Fang Zhang, Jun Xiao, Chi Zhang, Peng Chen, Xin Zheng, Xiaoyan XuAbstract:The special organelle-located MAVS, STING and TLR3 are important for clearing viral infections. Although TLR4 triggers NF-κB activation to produce pro-inflammatory cytokines for bacterial clearance, effectors with special organelle localization have not been identified. Here, we screened more than 280 E3 ubiquitin ligases and discovered that the endoplasmic reticulum-located Hrd1 regulates TLR4-induced inflammation during bacterial infection. Hrd1 interacts directly with the deubiquitinating enzyme Usp15. Unlike the classical function of Hrd1 in endoplasmic reticulum-associated degradation, Usp15 is not degraded but loses its deubiquitinating activity for IκBα deubiquitination, resulting in excessive NF-κB activation. Importantly, Hrd1 deficiency in macrophages protects mice against Lipopolysaccharide-Induced Septic Shock, and knockdown of Usp15 in Hrd1-knockout macrophages restores the reduced IL-6 production. This study proposes that there is crosstalk between Hrd1 and TLR4, thereby linking the endoplasmic reticulum–plasma membrane function during bacterial infection. Hrd1 is an endoplasmic reticulum-localized E3 ubiquitin ligase that inactivates Usp15 to promote inflammation during bacterial infection, and depletion of Hrd1 in macrophages protects mice from Septic Shock.
Kohsuke Takeda - One of the best experts on this subject based on the ideXlab platform.
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ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity
Nature Immunology, 2005Co-Authors: Atsushi Matsuzawa, Kaoru Saegusa, Takuya Noguchi, Chiharu Sadamitsu, Hideki Nishitoh, Shigenori Nagai, Shigeo Koyasu, Kunihiro Matsumoto, Kohsuke Takeda, Hidenori IchijoAbstract:Apoptosis signal–regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen-activated protein kinases. Here we used ASK1-deficient mice to show that ASK1 was selectively required for Lipopolysaccharide-Induced activation of p38 but not of Jnk or the transcription factor NF-κB. ASK1 was required for the induction of proinflammatory cytokines dependent on Toll-like receptor 4 (TLR4) but not TLR2 or other TLRs. Consistent with this, ASK1-deficient mice were resistant to Lipopolysaccharide-Induced Septic Shock. Lipopolysaccharide induced the production of intracellular reactive oxygen species, which was required for the formation of a complex of the adaptor molecule TRAF6 and ASK1 and subsequent activation of the ASK1-p38 pathway. Our data demonstrate that the reactive oxygen species–dependent TRAF6-ASK1-p38 axis is crucial for TLR4-mediated mammalian innate immunity.
Hideki Nishitoh - One of the best experts on this subject based on the ideXlab platform.
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ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity
Nature Immunology, 2005Co-Authors: Atsushi Matsuzawa, Kaoru Saegusa, Takuya Noguchi, Chiharu Sadamitsu, Hideki Nishitoh, Shigenori Nagai, Shigeo Koyasu, Kunihiro Matsumoto, Kohsuke Takeda, Hidenori IchijoAbstract:Apoptosis signal–regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen-activated protein kinases. Here we used ASK1-deficient mice to show that ASK1 was selectively required for Lipopolysaccharide-Induced activation of p38 but not of Jnk or the transcription factor NF-κB. ASK1 was required for the induction of proinflammatory cytokines dependent on Toll-like receptor 4 (TLR4) but not TLR2 or other TLRs. Consistent with this, ASK1-deficient mice were resistant to Lipopolysaccharide-Induced Septic Shock. Lipopolysaccharide induced the production of intracellular reactive oxygen species, which was required for the formation of a complex of the adaptor molecule TRAF6 and ASK1 and subsequent activation of the ASK1-p38 pathway. Our data demonstrate that the reactive oxygen species–dependent TRAF6-ASK1-p38 axis is crucial for TLR4-mediated mammalian innate immunity.