※一部利用できない機能があります
| 1.
論文 |
論文
|
中西, 義信 ; Nakanishi, Yoshinobu
概要:
金沢大学医薬保健研究域薬学系
|
||||
| 2.
論文 |
論文
|
Nainu, Firzan ; Shiratsuchi, Akiko ; Nakanishi, Yoshinobu ; 白土, 明子 ; 中西, 義信
概要:
金沢大学医薬保健研究域薬学系<br />Viruses are infectious entities that hijack host replication machineries to produce their progeny, r
…
esulting, in most cases, in disease and, sometimes, in death in infected host organisms. Hosts are equipped with an array of defense mechanisms that span from innate to adaptive as well as from humoral to cellular immune responses. We previously demonstrated that mouse cells underwent apoptosis in response to influenza virus infection. These apoptotic, virus-infected cells were then targeted for engulfment by macrophages and neutrophils. We more recently reported similar findings in the fruit fly Drosophila melanogaster, which lacks adaptive immunity, after an infection with Drosophila C virus. In these experiments, the inhibition of phagocytosis led to severe influenza pathologies in mice and early death in Drosophila. Therefore, the induction of apoptosis and subsequent phagocytosis of virus-infected cells appear to be an antiviral innate immune mechanism that is conserved among multicellular organisms. We herein discuss the underlying mechanisms and significance of the apoptosis-dependent phagocytosis of virus-infected cells. Investigations on the molecular and cellular features responsible for this underrepresented virus-host interaction may provide a promising avenue for the discovery of novel substances that are targeted in medical treatments against virus-induced intractable diseases. © 2017 Nainu, Shiratsuchi and Nakanishi.
続きを見る
|
||||
| 3.
論文 |
論文
|
Okada, Ryo ; Nagaosa, Kazushige ; Kuraishi, Takayuki ; Nakayama, Hiroshi ; Yamamoto, Naoko ; Nakagawa, Yukiko ; Dohmae, Naoshi ; Shiratsuchi, Akiko ; Nakanishi, Yoshinobu
概要:
To elucidate the actions of Draper, a receptor responsible for the phagocytic clearance of apoptotic cells in Drosophila
…
, we isolated proteins that bind to the extracellular region of Draper using affinity chromatography. One of those proteins has been identified to be an uncharacterized protein called Drosophila melanogaster calcium-binding protein 1 (DmCaBP1). This protein containing the thioredoxin-like domain resided in the endoplasmic reticulum and seemed to be expressed ubiquitously throughout the development of Drosophila. DmCaBP1 was externalized without truncation after the induction of apoptosis somewhat prior to chromatin condensation and DNA cleavage in a manner dependent on the activity of caspases. A recombinant DmCaBP1 protein bound to both apoptotic cells and a hemocyte-derived cell line expressing Draper. Forced expression of DmCaBP1 at the cell surface made non-apoptotic cells susceptible to phagocytosis. Flies deficient in DmCaBP1 expression developed normally and showed Draper-mediated pruning of larval axons, but a defect in the phagocytosis of apoptotic cells in embryos was observed. Loss of Pretaporter, a previously identified ligand for Draper, did not cause a further decrease in the level of phagocytosis in DmCaBP1-lacking embryos. These results collectively suggest that the endoplasmic reticulum protein DmCaBP1 is externalized upon the induction of apoptosis and serves as a tethering molecule to connect apoptotic cells and phagocytes for effective phagocytosis to occur. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
続きを見る
|
||||
| 4.
論文 |
論文
|
Kong, Qingquan ; Nakai, Yuji ; Kuroda, Nanae ; Shiratsuchi, Akiko ; Nagaosa, Kaz ; Nakanishi, Yoshinobu
概要:
Interaction between the host and pathogen determines the fate of both organisms during the infectious state. The host is
…
equipped with a battery of immune reactions, while the pathogen displays a variety of mechanisms to compromise host immunity. Although bacteria alter their pattern of gene expression in host organisms, studies to elucidate the mechanism behind this are only in their infancy. We here examined the possibility that host immune proteins directly participate in the change of gene expression in bacteria. Escherichia coli was treated with a mixture of the extracellular region of peptidoglycan recognition protein (PGRP)-LC and the antimicrobial peptide attacin of Drosophila, and subjected to DNA microarray analysis for mRNA repertoire. We identified 133 annotated genes whose mRNA increased after the treatment, and at least four of them were induced in response to PGRP-LC. One such gene, lipoprotein-encoding nlpI, showed a transient increase of mRNA in adult flies depending on PGRP-LC but not PGRP-LE. NlpI-lacking E. coli had a lowered growth rate and/or viability in flies than the parental strain. These results suggest that a host immune receptor triggers a change of gene expression in bacteria simultaneously with their recognition and induction of immune responses. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
続きを見る
|
||||
| 5.
論文 |
論文
|
Nonaka, Saori ; Ando, Yuki ; Kanetani, Takuto ; Hoshi, Chiharu ; Nakai, Yuji ; Nainu, Firzan ; Nagaosa, Kaz ; Shiratsuchi, Akiko ; Nakanishi, Yoshinobu
概要:
The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for elim
…
inating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocytespecific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.<br />Embargo Period 12 months
続きを見る
|
||||
| 6.
論文 |
論文
|
6. Inhibition of phagocytic killing of Escherichia coli in Drosophila Hemocytes by RNA Chaperone Hfq
Shiratsuchi, Akiko ; Nitta, Mao ; Kuroda, Ayumi ; Komiyama, Chiharu ; Gawasawa, Mitsuko ; Shimamoto, Naoto ; Tuan, Tran Quoc ; Morita, Teppei ; Aiba, Hiroji ; Nakanishi, Yoshinobu
概要:
An RNA chaperone of Escherichia coli, called host factor required for phage Qb RNA replication (Hfq), forms a complex wi
…
th small noncoding RNAs to facilitate their binding to target mRNA for the alteration of translation efficiency and stability. Although the role of Hfq in the virulence and drug resistance of bacteria has been suggested, how this RNA chaperone controls the infectious state remains unknown. In the present study, we addressed this issue using Drosophila melanogaster as a host for bacterial infection. In an assay for abdominal infection using adult flies, an E. coli strain with mutation in hfq was eliminated earlier, whereas flies survived longer compared with infection with a parental strain. The same was true with flies deficient in humoral responses, but the mutant phenotypes were not observed when a fly line with impaired hemocyte phagocytosis was infected. The results from an assay for phagocytosis in vitro revealed that Hfq inhibits the killing of E. coli by Drosophila phagocytes after engulfment. Furthermore, Hfq seemed to exert this action partly through enhancing the expression of s38, a stress-responsive s factor that was previously shown to be involved in the inhibition of phagocytic killing of E. coli, by a posttranscriptional mechanism. Our study indicates that the RNA chaperone Hfq contributes to the persistent infection of E. coli by maintaining the expression of bacterial genes, including one coding for s38, that help bacteria evade host immunity. ©2016 by The American Association of Immunologists, Inc.<br />Embargo Period 12 months
続きを見る
|
||||
| 7.
論文 |
論文
|
Nakanishi, Yoshinobu ; Nagaosa, Kazushige ; Shiratsuchi, Akiko
概要:
金沢大学医薬保健研究域薬学系<br />Cells that have become unwanted need to be promptly, selectively, and safely removed. This is made p
…
ossible by apoptosis-dependent phagocytosis, in which cells unnecessary, obstructive, or dangerous to organisms are induced to undergo apoptosis so that they are earmarked for phagocytosis. The phagocytic elimination occurs so quickly that cells with hallmarks of apoptosis are barely detectable in vivo. The removal of particular types of cells at appropriate stages of development not only contributes to the disposal of spent cells, the creation of space for morphogenesis, and the exclusion of pathogenic or noxious cells, but seems to actively control tissue renewal, tissue remodeling, tissue function, and pathogenic state. This event thus plays an indispensable role in the maintenance of animal development and tissue homeostasis. © 2011 The Authors. Journal compilation © 2011 Japanese Society of Developmental Biologists.
続きを見る
|
||||
| 8.
論文 |
論文
|
Takizawa, Takenori ; Tatematsu, Chizuru ; Nakanishi, Yoshinobu
概要:
金沢大学医薬保健研究域薬学系<br />PKR is an interferon-inducible, double-stranded (ds) RNA-activated serine/threonine protein kinase,
…
and has been shown to play roles in viral pathogenesis, cell growth and apoptosis. We expressed PKR as a fusion protein with enhanced jellyfish green fluorescence protein (EGFP) in human embryonic kidney 293 cells to visualize the effect of PKR transfection. The EGFP-fusion construct with wild-type PKR showed both auto- and substrate-phosphorylation activities independent of dsRNA, indicating EGFP-PKR is constitutively active. The EGFP-construct with a mutant PKR with the first RNA binding domain deleted still possessed kinase activities. On the other hand, the EGFP-fusion with a catalytically inactive mutant of PKR with the substitution of K at 296 with R, which has been shown to have tumorigenic properties, did not possess kinase activities. Transfection of the constitutive active forms of EGFP-PKR constructs induced apoptosis in 293 cells without dsRNA, whereas the EGFP-fusion with the catalytically inactive mutant did not cause apoptosis but rather protected cells from Fas-induced cell death. In addition, Fas-stimulation increased endogenous PKR activities. These results constitute evidence that PKR is sufficient to induce apoptosis, and plays a role in Fas-mediated apoptosis.
続きを見る
|
||||
| 9.
論文 |
論文
|
Shiratsuchi, Akiko ; Watanabe, Ikuko ; Ju, Jin-Sung ; Lee, Bok Luel ; Nakanishi, Yoshinobu
概要:
金沢大学医薬保健研究域薬学系<br />Mannose-binding lectin (MBL) exists in the serum as a complex with MBL-associated serine protease (M
…
ASP). A recent paper described how MASP-free recombinant rat MBL stimulates the phagocytosis of Escherichia coli and Staphylococcus aureus by rat Kupffer cells through an increase in the level of a phagocytosis receptor. We have examined the effect of human MBL on the phagocytic action of human macrophages. Purified recombinant human MBL stimulated the phagocytosis of E. coli by THP-1 macrophages, leaving that of latex beads, apoptotic human cells, zymosan particles or S. aureus unchanged. This stimulatory effect was observed when either phagocytes or targets were preincubated with MBL. Furthermore, MBL bound to THP-1 macrophages as well as to E. coli, but not to S. aureus, through lipid A. These results indicated that human MBL in the absence of MASP stimulates macrophage phagocytosis of E. coli by bridging targets and phagocytes. © 2008 The Authors.全文公開200908
続きを見る
|
||||
| 10.
論文 |
論文
|
Nakanishi, Yoshinobu ; Hashimoto, Yumi ; Takizawa, Takenori ; Shiratsuchi, Akiko
概要:
金沢大学医薬保健研究域薬学系<br />Influenza virus-infected cells are induced to undergo apoptosis and become susceptible to phagocytos
…
is. Data from our in vitro and in vivo experiments have suggested that 1) alveolar macrophages and neutrophils phagocytose influenza virus-infected cells in an apoptosis-dependent manner; 2) the membrane phospholipid phosphatidylserine and viral neuraminidase-processed carbohydrates at the surface of target cells and phagocytes, respectively, are involved in the association of the two types of cells; and 3) phagocytic elimination of virus-infected cells leads to a reduction in the pathogenesis of influenza. These findings could lead to the development of a novel antiviral agent against influenza. © 2008 Bentham Science Publishers Ltd.全文公開200906
続きを見る
|
