Toll-like receptors are temporally involved in host defense (2004)
Weiss, David S., Raupach, Bärbel, Takeda, Kiyoshi, Akira, Shizuo, Zychlinsky, Arturo
Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality
Takeda, Kiyoshi, Noguchi, Koichi, Shi, Wei, Tanaka, Takashi, Matsumoto, Makoto, Yoshida, Nobuaki, ...
Signal transducer and activator of transcription (STAT) proteins have been shown to mediate biological actions in response to cytokines. Stat3, a member of the STAT family, is activated by a variety...
Enhanced resistance in STAT6-deficient mice to infection with ectromelia virus
Mahalingam, Surendran, Karupiah, Gunasegaran, Takeda, Kiyoshi, Akira, Shizuo, Matthaei, Klaus I., Foster, Paul S.
We inoculated BALB/c mice deficient in STAT6 (STAT6−/−) and their wild-type (wt) littermates (STAT6+/+) with the natural mouse pathogen, ectromelia virus (EV). STAT6−/− mice exhibited...
Oyadomari, Seiichi, Takeda, Kiyoshi, Takiguchi, Masaki, Gotoh, Tomomi, Matsumoto, Makoto, Wada, Ikuo, ...
Excessive nitric oxide (NO) production in cytokine-activated β cells has been implicated in β cell disruption in type 1 diabetes. β cells are very vulnerable to NO-induced apoptosis. However, the...
Okuda, Tsukasa, Takeda, Kiyoshi, Fujita, Yasuko, Nishimura, Motohiro, Yagyu, Shigeki, Yoshida, Makie, ...
AML1 is one of the most frequently mutated genes associated with human acute leukemia and encodes the DNA-binding subunit of the heterodimering transcriptional factor complex, core-binding factor...
Ohkusu, Kazunobu, Yoshimoto, Tomohiro, Takeda, Kiyoshi, Ogura, Takeharu, Kashiwamura, Shin-ichiro, Iwakura, Yoichiro, ...
Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in natural killer cell activation and the T helper 1 (Th1) cell response, particularly in collaboration with IL-12....
Nomi, Masashi, Oishi, Isao, Kani, Shuichi, Suzuki, Hiroaki, Matsuda, Takeru, Yoda, Akinori, ...
The mammalian Ror family of receptor tyrosine kinases consists of two structurally related proteins, Ror1 and Ror2. We have shown that mRor2-deficient mice exhibit widespread skeletal abnormalities,...
Kawakami, Kazuyoshi, Kinjo, Yuki, Yara, Satomi, Uezu, Kaori, Koguchi, Yoshinobu, Tohyama, Masaki, ...
We showed recently that activation of Vα14+ natural killer T cells (NKT cells) by α-galactosylceramide (α-GalCer) resulted in increased gamma interferon (IFN-γ) production and host resistance to...
ZIP Kinase, a Novel Serine/Threonine Kinase Which Mediates Apoptosis
Kawai, Taro, Matsumoto, Makoto, Takeda, Kiyoshi, Sanjo, Hideki, Akira, Shizuo
We have identified a novel serine/threonine kinase, designated ZIP kinase, which mediates apoptosis. ZIP kinase contains a leucine zipper structure at its C terminus, in addition to a kinase domain...
Role of Interleukin-18 (IL-18) in Mycobacterial Infection in IL-18-Gene-Disrupted Mice
Sugawara, Isamu, Yamada, Hiroyuki, Kaneko, Hirotaka, Mizuno, Satoru, Takeda, Kiyoshi, Akira, Shizuo
Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-γ), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-α),...
Konishi, Hiroshi, Tsutsui, Hiroko, Murakami, Takaaki, Yumikura-Futatsugi, Shizue, Yamanaka, Kei-ichi, Tanaka, Minoru, ...
Atopic dermatitis (AD) is a pruritic inflammatory skin disease. Because IL-18 directly stimulates T cells and mast cells to release AD-associated molecules, Th2 cytokines, and histamine, we...
TAB2 Is Essential for Prevention of Apoptosis in Fetal Liver but Not for Interleukin-1 Signaling
Sanjo, Hideki, Takeda, Kiyoshi, Tsujimura, Tohru, Ninomiya-Tsuji, Jun, Matsumoto, Kunihiro, Akira, Shizuo
The proinflammatory cytokine interleukin-1 (IL-1) transmits a signal via several critical cytoplasmic proteins such as MyD88, IRAKs and TRAF6. Recently, serine/threonine kinase TAK1 and TAK1 binding...
Targeted disruption of the Chop gene delays endoplasmic reticulum stress–mediated diabetes
Oyadomari, Seiichi, Koizumi, Akio, Takeda, Kiyoshi, Gotoh, Tomomi, Akira, Shizuo, Araki, Eiichi, ...
Overload of pancreatic β cells in conditions such as hyperglycemia, obesity, and long-term treatment with sulfonylureas leads to β cell exhaustion and type 2 diabetes. Because β cell mass declines...
Interleukin-18 Impairs the Pulmonary Host Response to Pseudomonas aeruginosa
Schultz, Marc J., Knapp, Sylvia, Florquin, Sandrine, Pater, Jennie, Takeda, Kiyoshi, Akira, Shizuo, ...
Interleukin-18 (IL-18) is a potent cytokine with many different proinflammatory activities. To study the role of IL-18 in the pathogenesis of Pseudomonas pneumonia, IL-18-deficient (IL-18−/−) and...
Kobayashi, Masaya, Kweon, Mi-Na, Kuwata, Hirotaka, Schreiber, Robert D., Kiyono, Hiroshi, Takeda, Kiyoshi, ...
Stat3 plays an essential role in IL-10 signaling pathways. A myeloid cell-specific deletion of Stat3 resulted in inflammatory cytokine production and development of chronic enterocolitis with...
Kataoka, Naoaki, Tokiwa, Yutaka, Tanaka, Yasuo, Fujiki, Kiichi, Taroda, Hiroyuki, Takeda, Kiyoshi
Characteristic sludge ecosystems arising in anaerobic membrane bioreactors of three pilot-scale plants treating low-strength (less than 1 g of biological oxygen demand per liter) sewage or...
Rubber-Degrading Enzyme from a Bacterial Culture
Tsuchii, Akio, Takeda, Kiyoshi
Rubber-degrading activity was found in the extracellular culture medium of Xanthomonas sp. strain 35Y which was grown on natural rubber latex. Natural rubber in the latex state was degraded by the...
Kataoka, Naoaki, Tokiwa, Yutaka, Takeda, Kiyoshi
Methanogenic fluorescent colonies can be clearly identified on roll tubes by using an epifluorescence microscope equipped with a × 2 objective. Methanogenic and nonmethanogenic colonies could be...
Integral role of Noxa in p53-mediated apoptotic response
Shibue, Tsukasa, Takeda, Kiyoshi, Oda, Eri, Tanaka, Hiroshi, Murasawa, Hideki, Takaoka, Akinori, ...
The tumor suppressor p53 exerts its versatile function to maintain the genomic integrity of a cell, and the life of cancerous cells with DNA damage is often terminated by induction of apoptosis. We...
Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms
Haga, Sanae, Terui, Keita, Zhang, Hui Qi, Enosawa, Shin, Ogawa, Wataru, Inoue, Hiroshi, ...
Signal transducer and activator of transcription-3 (Stat3) is one of the most important molecules involved in the initiation of liver development and regeneration. In order to investigate the...
Interleukin-18 Facilitates the Early Antimicrobial Host Response to Escherichia coli Peritonitis
Weijer, Sebastiaan, Sewnath, Miguel E., De Vos, Alex F., Florquin, Sandrine, Sluis, Koen Van Der, Gouma, Dirk J., ...
To determine the role of endogenous interleukin-18 (IL-18) during peritonitis, IL-18 gene-deficient (IL-18 KO) mice and wild-type mice were intraperitoneally (i.p.) infected with Escherichia coli,...
Microbial Degradation of Natural Rubber Vulcanizates
Tsuchii, Akio, Suzuki, Tomoo, Takeda, Kiyoshi
An actinomycete, Nocardia sp. strain 835A, grows well on unvulcanized natural rubber and synthetic isoprene rubber, but not on other types of synthetic rubber. Not only unvulcanized but also various...
Stat-3 is required for pulmonary homeostasis during hyperoxia
Hokuto, Isamu, Ikegami, Machiko, Yoshida, Mitsuhiro, Takeda, Kiyoshi, Akira, Shizuo, Perl, Anne-Karina T., ...
Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain...
Chapman, Rachel S., Lourenco, Paula C., Tonner, Elizabeth, Flint, David J., Selbert, Stefan, Takeda, Kiyoshi, ...
Mammary gland involution is characterized by extensive apoptosis of the epithelial cells. At the onset of involution, Stat3 is specifically activated. To address the function of this signaling...
Nakasone, Chikara, Kawakami, Kazuyoshi, Hoshino, Tomoaki, Kawase, Yusuke, Yokota, Koichi, Yoshino, Kohichiro, ...
We report that clearance of Pseudomonas aeruginosa, accumulation of neutrophils, and synthesis of tumor necrosis factor alpha and macrophage inflammatory protein 2 in the infected lung were not...
Yang, Rongcun, Martinez Murillo, Francisco, Cui, Hengmi, Blosser, Richard, Uematsu, Satoshi, Takeda, Kiyoshi, ...
Dendritic cells (DCs) link innate and adaptive immunity by sensing pathogens or vaccinogens and signaling a variety of defense responses. Since human papillomavirus type 16 L1 virus-like particles...
Akamine, Morikazu, Higa, Futoshi, Arakaki, Noriko, Kawakami, Kazuyoshi, Takeda, Kiyoshi, Akira, Shizuo, ...
The role of Toll-like receptors (TLRs) in innate immunity to Legionella pneumophila, a gram-negative facultative intracellular bacterium, was studied by using bone marrow-derived macrophages and...
PI3K integrates the action of insulin and leptin on hypothalamic neurons
Xu, Allison Wanting, Kaelin, Christopher B., Takeda, Kiyoshi, Akira, Shizuo, Schwartz, Michael W., Barsh, Gregory S.
Central control of energy balance depends on the ability of proopiomelanocortin (POMC) or agouti-related protein (Agrp) hypothalamic neurons to sense and respond to changes in peripheral energy...
Papillomavirus Capsid Mutation To Escape Dendritic Cell-Dependent Innate Immunity in Cervical Cancer
Yang, Rongcun, Wheeler, Cosette M., Chen, Xiaojiang, Uematsu, Satoshi, Takeda, Kiyoshi, Akira, Shizuo, ...
Infection with oncogenic human papillomaviruses (HPVs), typified by HPV type 16 (HPV16), is a necessary cause of cervical cancer. Prophylactic vaccination with HPV16 L1 virus-like particles (VLPs)...
MyD88, but Not Toll-Like Receptors 4 and 2, Is Required for Efficient Clearance of Brucella abortus
Weiss, David S., Takeda, Kiyoshi, Akira, Shizuo, Zychlinsky, Arturo, Moreno, Edgardo
It is not clear how the host initially recognizes and responds to infection by gram-negative pathogenic Brucella spp. It was previously shown (D. S. Weiss, B. Raupach, K. Takeda, S. Akira, and A....
Prion pathogenesis in the absence of Toll-like receptor signalling
Prinz, Marco, Heikenwalder, Mathias, Schwarz, Petra, Takeda, Kiyoshi, Akira, Shizuo, Aguzzi, Adriano
To reach the brain from peripheral sites, prions must colonize various cell types within the lymphoreticular compartment. However, no prion entry receptors are yet known. Toll-like receptors (TLRs)...
Miyatsuka, Takeshi, Kaneto, Hideaki, Shiraiwa, Toshihiko, Matsuoka, Taka-aki, Yamamoto, Kaoru, Kato, Ken, ...
The transcription factor pancreatic and duodenal homeobox factor 1 (PDX-1) is expressed in pancreatic progenitor cells. In exocrine pancreas, PDX-1 is down-regulated during late development, while...
Okuda, Yoshiko, Takahashi, Ichiro, Kim, Jin-Kyung, Ohta, Noriyuki, Iwatani, Kouichi, Iijima, Hideki, ...
Forbidden CD4+ββ T cells, which produce interleukin (IL)-4 predominantly, are a pathological subset in the development of colitis in T-cell receptor α chain (TCRα)-deficient mice. Stimulation of...
Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency
Yamamoto, Masahiro, Uematsu, Satoshi, Okamoto, Toru, Matsuura, Yoshiharu, Sato, Shintaro, Kumar, Himanshu, ...
Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream signal transduction pathways that culminate in the activation of nuclear factor κB (NF-κB) and...
Sato, Nobuaki, Takahashi, Naoyuki, Suda, Koji, Nakamura, Midori, Yamaki, Mariko, Ninomiya, Tadashi, ...
Myeloid differentiation factor 88 (MyD88) plays essential roles in the signaling of the Toll/interleukin (IL)-1 receptor family. Toll–IL-1 receptor domain-containing adaptor inducing interferon-β...
Hemmi, Hiroaki, Takeuchi, Osamu, Sato, Shintaro, Yamamoto, Masahiro, Kaisho, Tsuneyasu, Sanjo, Hideki, ...
Viral infection and stimulation with lipopolysaccharide (LPS) or double stranded RNA (dsRNA) induce phosphorylation of interferon (IFN) regulatory factor (IRF)-3 and its translocation to the nucleus,...
Proteolytic Processing of Stat6 Signaling in Mast Cells as a Negative Regulatory Mechanism
Suzuki, Kotaro, Nakajima, Hiroshi, Kagami, Shin-ichiro, Suto, Akira, Ikeda, Kei, Hirose, Koichi, ...
Accumulating evidence has shown the importance of Stat6-mediated signaling in allergic diseases. In this study, we show a novel regulatory mechanism of Stat6-mediated signaling in mast cells. When...
Shi, Shuangping, Nathan, Carl, Schnappinger, Dirk, Drenkow, Jörg, Fuortes, Michele, Block, Ellen, ...
Macrophages are activated from a resting state by a combination of cytokines and microbial products. Microbes are often sensed through Toll-like receptors signaling through MyD88. We used large-scale...
Yokozeki, Hiroo, Ghoreishi, Mehran, Takagawa, Shinsuke, Takayama, Kaoru, Satoh, Takahiro, Katayama, Ichiro, ...
Contact hypersensitivity (CHS) is thought to be mainly associated with the activation of T helper type 1 (Th1) cells. However, there is also evidence that Th2 cells or Th2 cytokines play a role in...
Matsushima, Akemi, Kaisho, Tsuneyasu, Rennert, Paul D., Nakano, Hiroyasu, Kurosawa, Kyoko, Uchida, Daisuke, ...
Both nuclear factor (NF)-κB–inducing kinase (NIK) and inhibitor of κB (IκB) kinase (IKK) have been implicated as essential components for NF-κB activation in response to many external stimuli....
Helmby, Helena, Takeda, Kiyoshi, Akira, Shizuo, Grencis, Richard K.
Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th) 2 type response involving interleukin (IL)-4 and IL-13. Here we show that Th1 response–associated...
Essential Immunoregulatory Role for BCAP in B Cell Development and Function
Yamazaki, Tetsuo, Takeda, Kiyoshi, Gotoh, Kumiko, Takeshima, Hiroshi, Akira, Shizuo, Kurosaki, Tomohiro
BCAP was recently cloned as a binding molecule to phosphoinositide 3-kinase (PI3K). To investigate the role of BCAP, mutant mice deficient in BCAP were generated. While BCAP-deficient mice are...
Hoshino, Katsuaki, Kashiwamura, Shin-ichiro, Kuribayashi, Kozo, Kodama, Taku, Tsujimura, Tohru, Nakanishi, Kenji, ...
T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells....
Kaisho, Tsuneyasu, Tsutsui, Hiroko, Tanaka, Takashi, Tsujimura, Tohru, Takeda, Kiyoshi, Kawai, Taro, ...
We have investigated in vivo roles of CCAAT/enhancer binding protein γ (C/EBPγ) by gene targeting. C/EBPγ-deficient (C/EBPγ2/−) mice showed a high mortality rate within 48 h after birth. To...
Iκb Kinase α Is Essential for Mature B Cell Development and Function
Kaisho, Tsuneyasu, Takeda, Kiyoshi, Tsujimura, Tohru, Kawai, Taro, Nomura, Fumiko, Terada, Nobuyuki, ...
IκB kinase (IKK) α and β phosphorylate IκB proteins and activate the transcription factor, nuclear factor (NF)-κB. Although both are highly homologous kinases, gene targeting experiments...
Cis3/Socs3/Ssi3 Plays a Negative Regulatory Role in Stat3 Activation and Intestinal Inflammation
Suzuki, Asuka, Hanada, Toshikatsu, Mitsuyama, Keiichi, Yoshida, Takafumi, Kamizono, Shintaro, Hoshino, Tomoaki, ...
Immune and inflammatory systems are controlled by multiple cytokines, including interleukins (ILs) and interferons. These cytokines exert their biological functions through Janus tyrosine kinases and...
Akimoto, Toshihiko, Numata, Fumio, Tamura, Misato, Takata, Yoshimi, Higashida, Noriko, Takashi, Tohru, ...
Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4–mediated responses, including class switching to IgE and induction of type 2 T helper cells. To...
Schweizer, Ulrich, Gunnersen, Jennifer, Karch, Christoph, Wiese, Stefan, Holtmann, Bettina, Takeda, Kiyoshi, ...
Members of the ciliary neurotrophic factor (CNTF)/leukemia inhibitory factor (LIF)/cardiotrophin gene family are potent survival factors for embryonic and lesioned motoneurons. These factors act via...