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Dai Miyazaki

Publications and source records attributed to Dai Miyazaki.

7 recordsLinked to original sources
PubMed2005

CCR5 chemokine receptor mediates recruitment of MHC class II-positive Langerhans cells in the mouse corneal epithelium.

PURPOSE: To characterize the chemokines and chemokine receptors that mediate the effect of proinflammatory cytokines, interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, on the recruitment of MHC class II(+) Langerhans cells (LCs) in the corneal epithelium. METHODS: A standard model for corneal LC recruitment, application of cautery to the central corneal surface was used, and the differential gene expression levels of a panel of chemokines and chemokine receptors were determined by RNase protection assay. Chemokine receptor-knockout mice were used to evaluate the recruitment of MHC class II(+) LCs to the corneal epithelium. To determine the sensitivity of selected chemokines to IL-1 and TNF-alpha stimulation, the chemokine gene expression pattern was analyzed after blockade of IL-1 and TNF receptors. RESULTS: CCR1, -2, and -5 were overexpressed in corneas after cauterization. Topical administration of soluble TNF receptor I and IL-1 receptor antagonist, which abrogated corneal LC recruitment, significantly suppressed the gene transcription levels of the ligands of CCR1 and/or -5, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. The recruitment of major histocompatibility complex (MHC) class II(+) LC was significantly suppressed in CCR5(-/-) mice and blockade of RANTES and MIP-1beta, but not in CCR1(-/-), CCR2(-/-)/MIP-1alpha(-/-), or MIP-1alpha(-/-) mice. The evaluation of epithelial CD11c(+) LC cells by confocal microscopy revealed coexpression for CCR5 primarily among B7(-) (CD80(-)/CD86(-)) subsets of these LCs but not among the mature B7(+) subsets of CD11c(+) LCs. CONCLUSIONS: These data suggest that CCR5 plays a critical role in mediating recruitment and mobilization of MHC class II(+) LCs into the corneal epithelium. Targeting CCR5 and its ligands may be a new strategy for modulating immunity.

Animals↗
PubMed2005

Macrophage inflammatory protein-1alpha as a costimulatory signal for mast cell-mediated immediate hypersensitivity reactions.

Regulation of the immune response requires the cooperation of multiple signals in the activation of effector cells. For example, T cells require signals emanating from both the TCR for antigen (upon recognition of MHC/antigenic peptide) and receptors for costimulatory molecules (e.g., CD80 and CD60) for full activation. Here we show that IgE-mediated reactions in the conjunctiva also require multiple signals. Immediate hypersensitivity reactions in the conjunctiva were inhibited in mice deficient in macrophage inflammatory protein-1alpha (MIP-1alpha) despite normal numbers of tissue mast cells and no decrease in the levels of allergen-specific IgE. Treatment of sensitized animals with neutralizing antibodies with specificity for MIP-1alpha also inhibited hypersensitivity in the conjunctiva. In both cases (MIP-1alpha deficiency and antibody treatment), the degranulation of mast cells in situ was affected. In vitro sensitization assays showed that MIP-1alpha is indeed required for optimal mast cell degranulation, along with cross-linking of the high-affinity IgE receptor, FcepsilonRI. The data indicate that MIP-1alpha constitutes an important second signal for mast cell degranulation in the conjunctiva in vivo and consequently for acute-phase disease. Antagonizing the interaction of MIP-1alpha with its receptor CC chemokine receptor 1 (CCR1) or signal transduction from CCR1 may therefore prove to be effective as an antiinflammatory therapy on the ocular surface.

Animals↗
PubMed2005

Role of CC chemokines and their receptors in multiple aspects of mast cell biology: comparative protein profiling of FcepsilonRI- and/or CCR1-engaged mast cells using protein chip technology.

Apart from the FcepsilonRI-mediated mechanism, mast cells are activated by chemokines. Evidence has accumulated indicating that there is cross-talk between the FcepsilonRI-mediated signalling pathway and CC chemokine receptor (CCR)-mediated signalling pathways in mast cells. We have found that costimulation with IgE/antigen and CC chemokine ligand 3 (CCL3) enhances degranulation but inhibits chemotaxis of rat basophilic leukaemia (RBL)-2H3 cells expressing human CCR1 (RBL-CCR1 cells). We hypothesize that this signalling cross-talk in mast cells may play important roles in the orchestration and focusing of the allergic response. In this study, we have sought information about global protein networks either enhanced or inhibited following cross-talk between the FcepsilonRI-mediated and CCR-mediated signalling pathways in mast cells. We believe this information may be useful for providing an understanding of mast cell function and in the establishment of new anti-inflammatory drugs for allergic diseases. Proteomics is a promising tool for studying protein profiles within biological samples and facilitates an understanding of the complex responses of an organism to a stimulus. Here, we show comparative data of protein profiles derived from FcepsilonRI-engaged and/or CCR1-engaged RBL-CCR1 cells using protein chip array technology, a proteomic technology. We also discuss our view of the role of CC chemokines and CCRs in regulating multiple aspects of mast cell biology.

Animals↗
PubMed2004

Roles of chemokines in ocular allergy and possible therapeutic strategies.

The mechanism of ocular surface allergy in the forms of atopic conjunctivitis and vernal keratoconjunctivitis has been highlighted by specific functions of chemokines. In the context of late-phase allergic responses, these molecules have key roles in recruitment and activation of leukocytes. Their interaction with ligands is redundantly regulated; however, results from strategies to block subsets of chemokines have revealed unexpected or highly organized roles of these mediators. Exemplified by analyses of CCL11 function, current concepts of ocular allergy support CCL11 as central mediator. We emphasize the functions as modulator of mast cell activation/differentiation. With the prospect of understanding these functions, new modalities of drugs specifically developed to target CCL11/CCR3 interaction have been discussed.

Anti-Allergic Agents↗
PubMed2003

Chemokines: roles in leukocyte development, trafficking, and effector function.

Chemokines, representing a large superfamily of 8- to 15-kd proteins, were originally discovered through their ability to recruit various cell types into sites of inflammation. It is now clear that these molecules play a much wider role in immune homeostasis, playing key roles in driving the maturation, homing, and activation of leukocytes. In this review we analyze the roles chemokines play in the development, recruitment, and activation of leukocytes. Because signaling from the receptors drives these processes, signal transduction from chemokine receptors will also be reviewed. Taken together, we highlight the various points at which chemokines contribute to allergic inflammation and at which their targeting might contribute to new therapies for type I hypersensitivity reactions.

Cell Differentiation↗
PubMed2002

Murine NFX.1: isolation and characterization of its messenger RNA, mapping of its chromosomal location and assessment of its developmental expression.

We have previously isolated (by expression cloning) a human cDNA, termed NFX.1, encoding a nucleic acid-binding protein that interacts with the conserved X1 box cis-element first discovered in class II major histocompatibility complex (MHC) genes. Functional studies involving expression of NFX.1 and assessment of expression from class II reporter constructs and endogenous class II MHC genes indicated that the factor could repress transcription of class II MHC genes. Subsequent studies have extended the biological significance of the factor, indicating that it plays an important role in neuronal development. Indeed, the reiterated RING finger motifs in the central domain of the polypeptide strongly suggest that NF-XI is a probable E3 ubiquitin protein ligase, indicating that the protein may have multiple activities. Here we report the cloning of the mouse homologue of the human NfX.1 cDNA: m-Nfx.1. Comparison of the deduced primary sequence of mouse and human NFX.1 proteins shows very high homology and confirms that m-NFX.1 contains the conserved cysteine-rich DNA-binding motif first described in human NFX.1 (95% homology). Expression of MHC class II genes is substantially reduced following expression of m-NFX.1, which confirms that we have isolated the functional murine homologue of human NfX.1 cDNA. Further evidence comes from the mapping of m-Nfx.1 gene to the proximal region of mouse chromosome 4, a region syntenic to the location of human Nfx.1 (short arm of chromosome 9). Expression profiling shows that m-NFX.1 is expressed ubiquitously in both adult tissues and during development, supporting the hypothesis that it may have yet-undescribed roles in distinct biological processes.

Aging↗