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Narita, Japan

Gotoh M.,Ochanomizu University | Kotani N.,Research Institute of Biomolecule Metrology | Takahashi M.,Nihon Pharmaceutical Co. | Okada T.,Japan National Institute of Advanced Industrial Science and Technology | Ogawa Y.,Japan National Institute of Advanced Industrial Science and Technology
Cytologia | Year: 2010

The cytoplasmic tail (CT) of the influenza virus hemagglutinin (HA) consists of an amino acid sequence that is highly conserved among various subtypes of the influenza A virus. To study the effect of CT size on HA-mediated membrane fusion, we constructed a cDNA encoding a chimeric protein in which the size of CT of influenza virus HA (from A/Hong Kong/1/68; subtype H3) was enlarged by tagging with enhanced green fluorescent protein (EGFP). The EGFP-tagged HA (HA-EGFP) or wild-type HA was individually expressed in HeLa cells, and cell membrane fusion activities were examined using dual-labeled chicken red blood cells. The red blood cells were labeled with both lipidic and aqueous dyes to verify the fusion activity of the HA-EGFP at different steps of the fusion process: 1) lipid-mixing, 2) content-mixing and 3) fusion pore formation. Our data showed that the binding activity of HA towards red blood cells was not affected by enlargement of the CT of HA with EGFP. However, its lipid-mixing, subsequent content-mixing, and fusion pore formation activities were drastically impaired by the enlargement. Therefore, we conclude that CT size is crucial for progression from the binding step to the lipid-mixing step in the process of HAmediated membrane fusion. © 2010 The Japan Mendel Society.

Ujiie H.,Hokkaido University | Sasaoka T.,Hokkaido University | Sasaoka T.,Nihon Pharmaceutical Co. | Izumi K.,Hokkaido University | And 6 more authors.
Journal of Immunology | Year: 2014

Complement activation and subsequent recruitment of inflammatory cells at the dermal/epidermal junction are thought to be essential for blister formation in bullous pemphigoid (BP), an autoimmune blistering disease induced by autoantibodies against type XVII collagen (COL17); however, this theory does not fully explain the pathological features of BP. Recently, the involvement of complement-independent pathways has been proposed. To directly address the question of the necessity of the complement activation in blister formation, we generated C3-deficient COL17-humanized mice. First, we show that passive transfer of autoanti-bodies from BP patients induced blister formation in neonatal C3-deficient COL17-humanized mice without complement activation. By using newly generated human and murine mAbs against the pathogenic noncollagenous 16A domain of COL17 with high (human IgG1, murine IgG2), low (murine IgG1), or no (human IgG4) complement activation abilities, we demonstrate that the deposition of Abs, and not complements, is relevant to the induction of blister formation in neonatal and adult mice. Notably, passive transfer of BP autoantibodies reduced the amount of COL17 in lesional mice skin, as observed in cultured normal human keratinocytes treated with the same Abs. Moreover, the COL17 depletion was associated with a ubiquitin/proteasome pathway. In conclusion, the COL17 depletion induced by BP autoantibodies, and not complement activation, is essential for the blister formation under our experimental system. Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved.

Nihon Pharmaceutical Co. | Date: 2011-04-25

This is to provide a novel medicine and a food and a drink composition for treating aesthenopia excellent in improved effect of aesthenopia. The composition for the treatment of aesthenopia comprises chondroitin sulfate or a salt thereof.

Nihon Pharmaceutical Co. | Date: 2010-06-28

The present invention provides an autoantibody production inhibitor which can specifically suppress the autoantibodies and which can effectively prevent or treat the autoimmune disease of autoantibody type. According to the present invention, there is provided an autoantibody production inhibitor comprising, as an effective ingredient, a fusion protein which consists of a protein (X) containing a site recognized by autoantibodies which are a cause of the autoimmune disease of autoantibody type and a protein (A) containing a fragment which exhibits the antibody-dependent cellular cytotoxicity of the antibody heavy chain constant region.

Sasaki T.,Chiba University | Sasaki T.,Nihon Pharmaceutical Co. | Onodera A.,Chiba University | Hosokawa H.,Chiba University | And 9 more authors.
PLoS ONE | Year: 2013

Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity. © 2013 Sasaki et al.

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