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Innate Lymphoid Cells in the Airways: Their Functions and Regulators
Keisuke Orimo,Hirohisa Saito,Kenji Matsumoto,Hideaki Morita 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.3
Since the airways are constantly exposed to various pathogens and foreign antigens, various kinds of cells in the airways—including structural cells and immune cells—interact to form a precise defense system against pathogens and antigens that involve both innate immunity and acquired immunity. Accumulating evidence suggests that innate lymphoid cells (ILCs) play critical roles in the maintenance of tissue homeostasis, defense against pathogens and the pathogenesis of inflammatory diseases, especially at body surface mucosal sites such as the airways. ILCs are activated mainly by cytokines, lipid mediators and neuropeptides that are produced by surrounding cells, and they produce large amounts of cytokines that result in inflammation. In addition, ILCs can change their phenotype in response to stimuli from surrounding cells, which enables them to respond promptly to microenvironmental changes. ILCs exhibit substantial heterogeneity, with different phenotypes and functions depending on the organ and type of inflammation, presumably because of differences in microenvironments. Thus, ILCs may be a sensitive detector of microenvironmental changes, and analysis of their phenotype and function at local sites may enable us to better understand the microenvironment in airway diseases. In this review, we aimed to identify molecules that either positively or negatively influence the function and/or plasticity of ILCs and the sources of the molecules in the airways in order to examine the pathophysiology of airway inflammatory diseases and facilitate the issues to be solved.
( Kenichiro Okimoto ),( Makoto Arai ),( Hideaki Ishigami ),( Keiko Saito ),( Shoko Minemura ),( Daisuke Maruoka ),( Tomoaki Matsumura ),( Tomoo Nakagawa ),( Tatsuro Katsuno ),( Masaki Suzuki ),( Yukio 대한간학회 2018 Gut and Liver Vol.12 No.1
Background/Aims: Eosinophilic esophagitis (EoE) is often erroneously diagnosed as gastroesophageal reflux disease (GERD). The aim of this study is to investigate the prevalence of EoE and the expression of tight junction (TJ) proteins in patients with GERD symptoms. Methods: One hundred patients with GERD symptoms and 10 healthy controls were prospectively studied. Sixty-two patients had symptoms refractory to proton pump inhibitors (PPI). All patients underwent esophageal biopsy. Patients were diagnosed with EoE if the number of eosinophil granulocytes per high-power field was ≥15. Immunohistochemical analysis of TJ proteins (claudin-1, claudin-4, occludin, and zonula occludin-1 [ZO-1]) was performed. Results: EoE was diagnosed in six of 100 patients (6%) with GERD symptoms and in six patients (9.7%) of 62 patients with PPI-refractory GERD. Only one had typical EoE endoscopic findings. The proportion of ZO-1-positive cells was significantly lower in the lower than in the middle esophagus (56.0%±14.0% vs 66.0%±11.5%, p<0.05). There were no significant correlations between TJ protein expression and GERD symptoms. Conclusions: The prevalence of EoE among patients with PPI-refractory GERD is approximately 10%. Regardless of endoscopic findings, esophageal biopsy is crucial in diagnosing EoE. The disruption of ZO-1 expression in the lower esophagus is significantly associated with GERD symptoms. (Gut Liver 2018;12:30-37)
Yasuyuki Aoyagi,Yasushi Saito,Masayuki Kuroda,Sakiyo Asada,Hideaki Bujo,Shigeaki Tanaka,Shunichi Konno,Masami Tanio,Itsuko Ishii,Masayuki Aso 생화학분자생물학회 2011 Experimental and molecular medicine Vol.43 No.3
The development of clinically applicable scaffolds is important for the application of cell transplantation in various human diseases. The aims of this study are to evaluate fibrin glue in a novel protein replacement therapy using proliferative adipocytes and to develop a mouse model system to monitor the delivery of the transgene product into the blood and the fate of the transduced cells after transplantation. Proliferative adipocytes from mouse adipose tissue were transduced by a retroviral vector harboring the human lecithin-cholesterol acyltransferase (lcat) gene, and were subcutaneously transplanted into mice combined with fibrin glue. The lcat gene transduction efficiency and the subsequent secretion of the product in mouse adipocytes were enhanced using a protamine concentration of 500 μg/ml. Adipogenesis induction did not significantly affect the lcat gene-transduced cell survival after transplantation. Immunohistochemistry showed the ectopic enzyme production to persist for 28 days in the subcutaneously transplanted genetransduced adipocytes. The increased viability of transplanted cells with fibrin glue was accompanied with the decrease in apoptotic cell death. The immunodetectable serum LCAT levels in mice implanted with the fibrin glue were comparable with those observed in mice implanted with Matrigel, indicating that the transplanted lcat gene-transduced adipocytes survived and functioned in the transplanted spaces with fibrin glue as well as with Matrigel for 28 days. Thus,this in vivo system using fibrin is expected to serve as a good model to further improve the transplanted cell/scaffold conditions for the stable and durable cell-based replacement of defective proteins in patients with LCAT deficiency.
ALUMINUM BIAS SPUTTERING FOR FILM COVERAGE IMPROVEMENT
Kobayashi.Shigeru,Shimamura, Hideaki,Sakata, Masao,Fujita, Shouyou,Yajima, Akira,Saito, Hiroshi,Tateishi, Hideki,Sasaki, Shinji 대한전자공학회 1989 ICVC : International Conference on VLSI and CAD Vol.1 No.1
A filter was installed between the sputtering target and the substrate so as to reduce the aluminum deposition arriving with a shallow angle at the substrate in order to study the step coverage improvement by the bias application. It is deduced that the aluminum flowage occurs so that the surface energy is minimized around the via hole. Aluminum films deposited with the pulsed biasing were characterized in which the possible microstructual damage by argon bombardment is to be minimized. This biasing technique should provide with a better process for the step coverage improvement. A sputtering cathode was developed for aluminum bias sputtering which has a substrate current capability as high as 2A for a 5 inch wafer at the substrate voltage around-50V.
Aoyagi, Yasuyuki,Kuroda, Masayuki,Asada, Sakiyo,Bujo, Hideaki,Tanaka, Shigeaki,Konno, Shunichi,Tanio, Masami,Ishii, Itsuko,Aso, Masayuki,Saito, Yasushi Korean Society for Biochemistry and Molecular Bion 2011 Experimental and molecular medicine Vol.43 No.3
The development of clinically applicable scaffolds is important for the application of cell transplantation in various human diseases. The aims of this study are to evaluate fibrin glue in a novel protein replacement therapy using proliferative adipocytes and to develop a mouse model system to monitor the delivery of the transgene product into the blood and the fate of the transduced cells after transplantation. Proliferative adipocytes from mouse adipose tissue were transduced by a retroviral vector harboring the human lecithin- cholesterol acyltransferase ($lcat$) gene, and were subcutaneously transplanted into mice combined with fibrin glue. The $lcat$ gene transduction efficiency and the subsequent secretion of the product in mouse adipocytes were enhanced using a protamine concentration of $500{\mu}g/ml$. Adipogenesis induction did not significantly affect the $lcat$ gene-transduced cell survival after transplantation. Immunohistochemistry showed the ectopic enzyme production to persist for 28 days in the subcutaneously transplanted genetransduced adipocytes. The increased viability of transplanted cells with fibrin glue was accompanied with the decrease in apoptotic cell death. The immunodetectable serum LCAT levels in mice implanted with the fibrin glue were comparable with those observed in mice implanted with Matrigel, indicating that the transplanted $lcat$ gene-transduced adipocytes survived and functioned in the transplanted spaces with fibrin glue as well as with Matrigel for 28 days. Thus, this $in$ $vivo$ system using fibrin is expected to serve as a good model to further improve the transplanted cell/scaffold conditions for the stable and durable cell-based replacement of defective proteins in patients with LCAT deficiency.
Yoshitaka Fukaya,Yasuyuki Aoyagi,Sakiyo Asada,Yoshitaka Kubota,Yoshitaka Okamoto,Toshinori Nakayama,Yasushi Saito,Kaneshige Satoh,Masayuki Kuroda,Hideaki Bujo 생화학분자생물학회 2012 Experimental and molecular medicine Vol.44 No.5
Auto-transplantation of adipose tissue is commonly used for the treatment of tissue defects in plastic surgery. The survival of the transplanted adipose tissue is not always constant, and one of reasons is the accelerated apoptosis of the implanted preadipocytes. We have recently established highly homogeneous preadipocytes, named ccdPAs. The aim of the current study was to evaluate the regulation of the potency of platelet-rich plasma (PRP) on the apoptosis of ccdPAs in vitro. PRP stimulated the proliferation of the preadipocytes in a dose-dependent manner, and the stimulatory activity of 2% PRP was significantly higher than that of 2% FBS or 2% platelet-poor plasma (PPP). The presence of 2% PRP significantly inhibited serum starvation-or TNF-α/cycloheximide-induced apoptosis in comparison to 2% FBS or 2% PPP. DAPK1 and Bcl-2-interacting mediator of cell death (BIM) mRNAs were reduced in the preadipocytes cultured with 2% PRP in comparison to those cultured in 2% FBS. The gene expression levels were significantly higher in cells cultured without serum in comparison to cells cultured with 2% FBS, and the levels in the cells with 2% PRP were reduced to 5-10% of those in the cells without serum. These results indicated that ccdPAs exhibit anti-apoptotic activities, in addition to increased proliferation,when cultured in 2% PRP in comparison to the same concentration of FBS, and that this was accompanied with reduced levels of DAPK1 and BIM mRNA expression in in vitro culture. PRP may improve the outcome of transplantation of adipose tissue by enhancing the anti-apoptotic activities of the implanted preadipocytes.