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981.
Differential expression and subcellular localization of claudin-7, -8, -12, -13, and -15 along the mouse intestine. 总被引:7,自引:0,他引:7
982.
Oikawa T Kamimura Y Akiba H Yagita H Okumura K Takahashi H Zeniya M Tajiri H Azuma M 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(7):4281-4287
Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1 responses. We examined Tim-3 and its ligand expression as well as the effects of anti-Tim-3 mAb treatment in a murine model of acute graft-vs-host disease (aGVHD). In mice with aGVHD, Tim-3 expression was markedly up-regulated on splenic and hepatic CD4+ and CD8+ T cells, dendritic cells (DCs), and macrophages, and this was especially dramatic in hepatic CD8+ T cells. Both donor- and host-derived CD8+ T cells induced similar levels of Tim-3. Tim-3 ligand expression was also up-regulated in splenic T cells, DCs, and macrophages, but not in the hepatic lymphocytes. The administration of anti-Tim-3 mAbs accelerated aGVHD, as demonstrated by body weight loss, reduction in total splenocyte number, and infiltration of lymphocytes in the liver. IFN-gamma expression by splenic and hepatic CD4+ and CD8+ T cells was significantly augmented by anti-Tim-3 mAb treatment. In addition, the cytotoxicity against host alloantigen by donor CD8+ T cells was enhanced. These results demonstrate that the anti-Tim-3 treatment in aGVHD augmented the activation of effector T cells expressing IFN-gamma or exerting cytotoxicity. Our results suggest that Tim-3 may play a crucial role in the regulation of CD8+ T cells responsible for the maintenance of hepatic homeostasis and tolerance. 相似文献
983.
The matrix metalloproteinases (MMPs) are a family of proteases capable of degrading various components of the extracellular
matrix (ECM). Among them, the membrane type MMP–1 (MT1–MMP) has been shown to participate in the activation of MMP gelatinase
A (GelA), suggesting that they may function together in development and pathogenesis. Here, we have investigated the spatiotemporal
expression profiles of Xenopus laevis MT1–MMP and GelA genes during thyroid-hormone-dependent metamorphosis. We have focused our studies on two organs: (1) the
intestine, which undergoes first the degeneration of the tadpole epithelium through apoptosis and then the development of
adult epithelium and other tissues, and (2) the tail, which completely resorbs through programmed cell death. We show that
both MT1–MMP and GelA are upregulated in the intestine and tail when both organs undergo metamorphosis. Within the organs,
MT1–MMP and GelA are coexpressed in the connective tissues during both natural and thyroid-hormone-induced metamorphosis.
In addition, MT1–MMP (but not GelA) is also expressed in the longitudinal muscle cells of the metamorphosing intestine. These
results suggest that MT1–MMP and GelA function together in the ECM degradation or remodeling associated with metamorphosis
and that MT1–MMP has additional GelA–independent roles in the development of adult longitudinal muscle in the intestine.
This research was supported by the Intramural Research Program of the National Institute of Child Health and Human Development,
NIH. T. Hasebe and H. Matsuda were supported in part by JSPS (NIH) fellowships. 相似文献
984.
This study was designed to test the possibility that antimicrobial peptides could be derived from the genomic sequences of phage lysins. Using two lysins (D3 and PhiKZ) we selected and produced two putative peptides (X and Z, respectively) believed to possess antimicrobial properties based on their physicochemical characteristics. The data presented support this hypothesis in that the peptides and various analogs displayed antibacterial activity, bacteriostatic or bactericidal, either individually or upon combination. These putative peptides are believed to act by a mechanism of action resembling that of conventional antimicrobial peptides when judged by both structural and functional criteria. Thus, the peptides are shown to have the ability to form a helical structure, to bind to model bacterial membranes and permeabilize model liposomes. They also display rapid bactericidal kinetics and their antibacterial potency is increased upon amidation. The possible relevance of these results in contributing to potency of phage lysins is discussed. Such peptides may be used to design new potent antimicrobial compounds much needed in face of the ever threatening drug resistance problems. 相似文献
985.
A novel HSF1-mediated death pathway that is suppressed by heat shock proteins 总被引:6,自引:0,他引:6 下载免费PDF全文
Hayashida N Inouye S Fujimoto M Tanaka Y Izu H Takaki E Ichikawa H Rho J Nakai A 《The EMBO journal》2006,25(20):4773-4783
986.
Suh WK Wang S Duncan GS Miyazaki Y Cates E Walker T Gajewska BU Deenick E Dawicki W Okada H Wakeham A Itie A Watts TH Ohashi PS Jordana M Yoshida H Mak TW 《Molecular and cellular biology》2006,26(17):6403-6411
Members of the B7 family of cosignaling molecules regulate T-cell proliferation and effector functions by engaging cognate receptors on T cells. In vitro and in vivo blockade experiments indicated that B7-H4 (also known as B7S1 or B7x) inhibits proliferation, cytokine production, and cytotoxicity of T cells. B7-H4 binds to an unknown receptor(s) that is expressed on activated T cells. However, whether B7-H4 plays nonredundant immune regulatory roles in vivo has not been tested. We generated B7-H4-deficient mice to investigate the roles of B7-H4 during various immune reactions. Consistent with its inhibitory function in vitro, B7-H4-deficient mice mounted mildly augmented T-helper 1 (Th1) responses and displayed slightly lowered parasite burdens upon Leishmania major infection compared to the wild-type mice. However, the lack of B7-H4 did not affect hypersensitive inflammatory responses in the airway or skin that are induced by either Th1 or Th2 cells. Likewise, B7-H4-deficient mice developed normal cytotoxic T-lymphocyte reactions against viral infection. Thus, B7-H4 plays a negative regulatory role in vivo but the impact of B7-H4 deficiency is minimal. These results suggest that B7-H4 is one of multiple negative cosignaling molecules that collectively provide a fine-tuning mechanism for T-cell-mediated immune responses. 相似文献
987.
988.
We examined the structure-function relationships of residues in the fifth transmembrane domain (TM5) of the Na+/H+ antiporter A (NhaA) from Helicobacter pylori (HP NhaA) by cysteine scanning mutagenesis. TM5 contains two aspartate residues, Asp-171 and Asp-172, which are essential for antiporter activity. Thirty-five residues spanning the putative TM5 and adjacent loop regions were replaced by cysteines. Cysteines replacing Val-162, Ile-165, and Asp-172 were labeled with NEM, suggesting that these three residues are exposed to a hydrophilic cavity within the membrane. Other residues in the putative TM domain, including Asp-171, were not labeled. Inhibition of NEM labeling by the membrane impermeable reagent AMS suggests that Val-162 and Ile-165 are exposed to a water filled channel open to the cytoplasmic space, whereas Asp-172 is exposed to the periplasmic space. D171C and D172C mutants completely lost Na+/H+ and Li+/H+ antiporter activities, whereas other Cys replacements did not result in a significant loss of these activities. These results suggest that Asp-171 and Asp-172 and the surrounding residues of TM5 provide an essential structure for H+ binding and Na+ or Li+ exchange. A168C and Y183C showed markedly decreased antiporter activities at acidic pH, whereas their activities were higher at alkaline pH, suggesting that the conformation of TM5 also plays a crucial role in the HP NhaA-specific acidic pH antiporter activity. 相似文献
989.
Sueda S Li YQ Kondo H Kawarabayasi Y 《Biochemical and biophysical research communications》2006,344(1):155-159
Biotin protein ligase (BPL) is an enzyme mediating biotinylation of a specific lysine residue of the carboxyl carrier protein (BCCP) of biotin-dependent enzymes. We recently found that the substrate specificity of BPL from archaeon Sulfolobus tokodaii is totally different from those of many other organisms, in reflection of a difference in the local sequence of BCCP surrounding the canonical lysine residue. There is a conserved glycine residue in the biotin-binding site of Escherichia coli BPL, but this residue is replaced with alanine in S. tokodaii BPL. To test the notion that this substitution dictates the substrate specificity of the latter enzyme, this residue, Ala-43, was converted to glycine. The K(m) values of the resulting mutant, A43G, for substrates, were smaller than those of the wild type, suggesting that the residue in position 43 of BPL plays an important role in substrate binding. 相似文献
990.
Masaike T Suzuki T Tsunoda SP Konno H Yoshida M 《Biochemical and biophysical research communications》2006,342(3):800-807
A subcomplex of F0F1-ATP synthase (F0F1), alpha3beta3gamma, was shown to undergo the conformation(s) during ATP hydrolysis in which two of the three beta subunits have the "Closed" conformation simultaneously (CC conformation) [S.P. Tsunoda, E. Muneyuki, T. Amano, M. Yoshida, H. Noji, Cross-linking of two beta subunits in the closed conformation in F1-ATPase, J. Biol. Chem. 274 (1999) 5701-5706]. This was examined by the inter-subunit disulfide cross-linking between two mutant beta(I386C)s that was formed readily only when the enzyme was in the CC conformation. Here, we adopted the same method for the holoenzyme F0F1 from Bacillus PS3 and found that the CC conformation was generated during ATP hydrolysis but barely during ATP synthesis. The experiments using F0F1 with the epsilon subunit lacking C-terminal helices further suggest that this difference is related to dynamic nature of the epsilon subunit and that ATP synthesis is accelerated when it takes the pathway involving the CC conformation. 相似文献