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排序方式: 共有320条查询结果,搜索用时 15 毫秒
51.
Takahiro Ishikawa Hisakata Yamada Akiko Oyamada Fumi Goshima Yukihiro Nishiyama Yasunobu Yoshikai 《Journal of virology》2009,83(22):11777-11783
Herpes simplex virus type 2 (HSV-2) induces acute local infection followed by latent infection in the nervous system and often leads to the development of lethal encephalitis in immunocompromised hosts. The mechanisms of immune protection against lethal HSV-2 infection, however, have not been clarified. In this study, we examined the roles of Fas-Fas ligand (FasL) signaling in lethal infection with HSV-2 by using mice with mutated Fas (lpr) or FasL (gld) in C57BL/6 background. Both lpr and gld mice exhibited higher mortality than wild-type (WT) C57BL/6 mice after infection with virulent HSV-2 strain 186 and showed significantly increased viral titers in the spinal cord compared with WT mice 9 days after infection, just before the mice started to die. There were no differences in the numbers of CD4+ and CD8+ T cells infiltrated in the spinal cord or in the levels of HSV-2-specific gamma interferon produced by those cells in a comparison of lpr and WT mice 9 days after infection. Adoptive transfer studies demonstrated that CD4+ T cells from WT mice protected gld mice from lethal infection by HSV-2. Furthermore, CD4+ T cells infiltrated in the spinal cord of HSV-2-infected WT mice expressed functional FasL that induced apoptosis of Fas-expressing target cells in vitro. These results suggest that FasL-mediated cytotoxic activity of CD4+ T cells plays an important role in host defense against lethal infection with HSV-2.Fas-Fas ligand (FasL) signaling-induced apoptotic cell death has pleiotropic roles in T-cell-mediated host defense mechanisms. First, Fas and FasL are expressed on activated T cells and thereby limit their number by inducing suicide or fratricide. It is generally accepted that Fas-mediated activation-induced cell death plays a predominant role during chronic infection, whereas starvation-induced cell death mediated by the proapoptotic BH3-only subgroup of the Bcl-2 protein family is the main mechanism for T-cell death during termination of immune responses in acute infection (30). Fas-FasL signaling might also play a role in T-cell development, as suggested by an accumulation of T-cell receptor αβ-positive (TCR αβ+) CD4− CD8− T cells expressing B220 in lymphoid organs of mice with mutated Fas (lpr) or FasL (gld) although the origin and functions of such double-negative T cells are still a matter of debate (21). Lastly, Fas-FasL interaction can be directly involved in host defense by inducing apoptosis of infected cells to facilitate pathogen clearance (23). Therefore, the roles of Fas-FasL signaling in immune responses for host defense might vary depending on the pathogen.Herpes simplex virus type 2 (HSV-2) is an alphaherpesvirus that causes genital herpes, the most common viral sexually transmitted disease (29). After initial infection in the vaginal epithelium, HSV-2 invades local nerve termini, travels via retrograde axonal transport to neuronal cell bodies in sensory ganglia, and establishes latent infection (13). However, especially in neonates and immunocompromised hosts, HSV-2 can cause lethal central nervous system (CNS) infection, which indicates the importance of immune systems in limiting the pathogenicity of HSV-2. Immune responses against HSV-2 have been studied in various murine models using different strains of virus and routes of inoculation, with or without vaccination with an attenuated strain of HSV-2. In such vaccination models, CD4+ T cells producing gamma interferon (IFN-γ) predominantly conferred protection against challenge with a virulent strain of HSV-2 (11, 19), whereas various subsets of lymphocytes, including NK cells, NK T cells, and TCR γδ T cells as well as CD4+ T cells were reported to be involved in host defense against primary infection with virulent HSV-2 (3, 15, 24), in which IFN-γ also played an important role (9). Fas-FasL signaling was shown to be dispensable for the clearance of an attenuated strain of HSV-2, which lacks thymidine kinase and causes only transient mild vaginal pathologies but not neurologic diseases (6, 16). Similarly Fas-mediated apoptosis was not involved in the vaccination effect of the attenuated HSV-2 (11). However, the roles of Fas-FasL signaling in host defense against a virulent strain of HSV-2 have not been clarified.In this study, we examined the roles of Fas-FasL signaling in a murine model of HSV-2 infection by using a highly virulent HSV-2 strain 186 with lpr and gld mice. We found that FasL-Fas signaling plays an important role in host defense against lethal HSV-2 infection. 相似文献
52.
Masahiko Ito Fumi Mizoroki Kazunari Yamaguchi 《Biochemical and biophysical research communications》2009,390(2):269-272
Epidemiological data have indicated a close relationship between chronic HCV infection and non-Hodgkin’s B-cell lymphoma (B-NHL). In this study, functional phenotypes and gene expression profiles of PBMCs were analyzed in chronic hepatitis C (CHC) patients who developed B-NHL. The frequencies of effector CD8+ T cells and cytotoxic natural killer cells increased in CHC patients with B-NHL compared to those in CHC patients without B-NHL. These phenotypic changes may reflect the host’s immune response to neoplasia. The mRNA expression levels of several oncogenes increased in CHC patients without B-NHL, but were much higher in CHC patients with B-NHL, while mRNA levels of type I IFNs were decreased in CHC patients without B-NHL and were nearly negligible in CHC patients with B-NHL. Interestingly, the mRNA expression levels of activation-induced cytidine deaminase and caspase recruitment domain-containing proteins markedly increased in CHC patients without B-NHL but decreased in CHC patients with B-NHL. These results are discussed in view of the possible involvement of HCV infection in B-cell lymphomagenesis. 相似文献
53.
Background
Adipose tissues serve not only as a store for energy in the form of lipid, but also as endocrine tissues that regulates metabolic activities of the organism by secreting various kinds of hormones. Peroxisome proliferator activated receptor γ (PPARγ) is a key regulator of adipocyte differentiation that induces the expression of adipocyte-specific genes in preadipocytes and mediates their differentiation into adipocytes. Furthermore, PPARγ has an important role to maintain the physiological function of mature adipocyte by controlling expressions of various genes properly. Therefore, any reduction in amount and activity of PPARγ is linked to the pathogenesis of metabolic syndrome. 相似文献54.
55.
56.
Tokumi Maruyama Shigetada Kozai Fumi Sasaki 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1193-1203
Abstract A general procedure to obtain tetra-substituted uric acid by stepwise N-alkylation is described. 2,6-Dichloropurine (1) was condensed with 1-propanol by Mitsunobu reaction to give 9-propyl congener (2). Treatment of 2 with ammonia gave adenine derivative (4a), which was converted to the 8-oxoadenine (5b) in 3 steps. Methylation of 5b proceeded site-specifically to give 6-amino-2-chloro-7,8-dihydro-7-methyl-9-propylpurin-8-one (6) as a sole product. Compound 6 was successively treated with NaNO2 and iodomethane to give 2-chloro-1,6,7,8-tetrahydro-1,7-dimethyl-9-propylpurin-6,8-dione (9) accompanied by the O 6-methyl product (8) in 75% and 6.9%, respectively. After nucleophilic substitution of 9 with NaOAc, the product (11) was reacted with iodomethane to give the uric acid (12) and the 2-methoxy product (13) in 46% and 15.5%, respectively. However, the reaction of 11 with the benzylating agents gave only O-benzyl products (14a,b). 相似文献
57.
An Inducible Copper-Thiolate Complex in the Fern, Athyrium yokoscense: Involvement in Copper-Tolerance of the Fern 总被引:1,自引:0,他引:1
Nishizono Hiromi; Minemura Haruko; Suzuki Shizuo; Ishii Fumi 《Plant & cell physiology》1988,29(8):1345-1351
Two peaks of Cu-containing material were isolated from the solublecytoplasmic fraction of roots of Athyrium yokoscense, a fernwith a tolerance for heavy metals, by gel filtration on Bio-GelP-30 and Sephadex G-25. Peak I (apparent molecular weight 9.5kDa) was only observed in the case of ferns growing on Cu-contaminatedsoil. Peak II (apparent molecular weight 2 kDa) was found inextracts of ferns from both Cu-contaminated and uncontaminatedsoil. Peak I was induced in the fern collected from an uncontaminatedarea by cultivation in Cu-contaminated soil for 14 months. Theinduced Cu-binding complex present in peak I, therefore, maybe involved in mechanisms of Cu-tolerance in the fern. The complexwas purified by column chromatography on DEAE-cellulofine andsubsequent high-performance liquid chromatography. The purifiedcomplex contained a high percentage (26.8%) of cysteine, typicalof metal-binding peptides from plants. (Received June 1, 1988; Accepted September 12, 1988) 相似文献
58.
Fumi Ota Tetsuya Hirayama Yasuhiko Kizuka Yoshiki Yamaguchi Reiko Fujinawa Masahiro Nagata Hendra S. Ismanto Bernd Lepenies Jonas Aretz Christoph Rademacher Peter H. Seeberger Takashi Angata Shinobu Kitazume Keiichi Yoshida Tomoko Betsuyaku Kozui Kida Sho Yamasaki Naoyuki Taniguchi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(7):1592-1601
Background
Langerin, a C-type lectin receptor (CLR) expressed in a subset of dendritic cells (DCs), binds to glycan ligands for pathogen capture and clearance. Previous studies revealed that langerin has an unusual binding affinity toward 6-sulfated galactose (Gal), a structure primarily found in keratan sulfate (KS). However, details and biological outcomes of this interaction have not been characterized. Based on a recent discovery that the disaccharide L4, a KS component that contains 6-sulfo-Gal, exhibits anti-inflammatory activity in mouse lung, we hypothesized that L4-related compounds are useful tools for characterizing the langerin-ligand interactions and their therapeutic application.Methods
We performed binding analysis between purified long and short forms of langerin and a series of KS disaccharide components. We also chemically synthesized oligomeric derivatives of L4 to develop a new high-affinity ligand of langerin.Results
We show that the binding critically requires the 6-sulfation of Gal and that the long form of langerin displays higher affinity than the short form. The synthesized trimeric (also designated as triangle or Tri) and polymeric (pendant) L4 derivatives displayed over 1000-fold higher affinity toward langerin than monomeric L4. The pendant L4, but not the L4 monomer, was found to effectively transduce langerin signaling in a model cell system.Conclusions
L4 is a specific ligand for langerin. Oligomerization of L4 unit increased the affinity toward langerin.General significance
These results suggest that oligomeric L4 derivatives will be useful for clarifying the langerin functions and for the development of new glycan-based anti-inflammatory drugs. 相似文献59.
60.