A5019715351- Liver Disease Diagnosis and Treatment
- Liver Diseases and Immunity
- Liver physiology and pathology
- Diet, Metabolism, and Disease
- Immune Cell Function and Interaction
- Drug-Induced Hepatotoxicity and Protection
- Pediatric Hepatobiliary Diseases and Treatments
- Liver Disease and Transplantation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- T-cell and B-cell Immunology
- Drug Transport and Resistance Mechanisms
- Diabetes and associated disorders
- Diet and metabolism studies
- Systemic Lupus Erythematosus Research
- Inflammatory Bowel Disease
- Immune cells in cancer
- Pancreatitis Pathology and Treatment
- Pancreatic and Hepatic Oncology Research
- Adipose Tissue and Metabolism
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Endoplasmic Reticulum Stress and Disease
- Hepatitis B Virus Studies
- Viral-associated cancers and disorders
- Adipokines, Inflammation, and Metabolic Diseases
Tokushima University
2016-2025
Institute of Biomedical Science
2017-2025
Oita Medical Center
2024
Ehime Prefectural Central Hospital
2024
Photonic Science (United Kingdom)
2023
University of Toyama
2009-2021
Tokushima University Hospital
2020
University of California, Davis
1994-2016
Kanazawa University
1998-2016
Nagoya University
2015-2016
OBJECTIVE To characterize the phenotypic changes of adipose tissue macrophages (ATMs) under different conditions insulin sensitivity. RESEARCH DESIGN AND METHODS The number and expressions marker genes for M1 M2 from mouse epididymal fat were analyzed using flow cytometry after mice had been subjected to a high-fat diet (HFD) pioglitazone treatment. RESULTS Most CD11c-positive CD206-positive in clearly separated cytometry. exhibited completely gene expression patterns. Not only numbers ATMs...
Sclerosing cholangitis (SC) is a heterogeneous disease entity. Different etiologies such as choledocholithiasis, biliary tumor, or pericholangitis can manifest SC. Hepatic inflammatory pseudotumor (IP) rarely associated with SC (sclerosing hepatic pseudotumor; SC-hepatic IP), but sclerosing pancreatitis (SP) not infrequently bile duct lesions pancreatitis-associated cholangitis; SP-SC). In this study, we compared the histologic changes of hilar and extrahepatic (7 cases), IP (5 SP-SC typical...
Chronic sclerosing sialadenitis (CSS) is a cryptogenic tumor-like condition of the salivary gland(s). While immune-mediated processes are suspected in its pathogenesis, and CSS occasionally reported to be associated with pancreatitis, an IgG4-related disease, exact immunopathologic remain speculative. In this study, we examined clinicopathologic findings (12 cases) comparison sialolithiasis (8 Sjögren's syndrome (13 cases), tried clarify whether disease or not. Submandibular gland(s) were...
IL-5 is involved in a number of immune responses such as helminth infection and allergy. also plays roles innate immunity by maintaining B-1 B cells mucosal IgA production. However, the identity IL-5-producing has not been unambiguously characterized. In this report, we describe generation an reporter mouse identify non-T lymphoid that reside intestine, peritoneal cavity, lungs naive mice. They share many characteristics with natural helper cells, nuocytes, Ih2 including surface Ags...
Abstract Adipose tissue resident macrophages have important roles in the maintenance of homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like adipose systemic glucose inhibiting adipocyte progenitor proliferation via CD206/TGFβ signaling pathway. We CD206 + cells are primarily macrophages, ablation improves sensitivity, which was associated with an increased number smaller adipocytes. Mice genetically...
Inflammasome activation initiates the development of many inflammatory diseases, including obesity and type 2 diabetes. Therefore, agents that target discrete steps could represent very important drugs. We reported previously ILG, a chalcone from Glycyrrhiza uralensis, inhibits LPS-induced NF-κB activation. Here, we show ILG potently NLRP3 inflammasome, effect is independent its inhibitory potency on TLR4. The was stronger than parthenolide, known inhibitor inflammasome. GL, triterpenoid G....
CD4+CD25high regulatory T cells (Tregs) play a critical role in self-tolerance, as seen murine autoimmunity. Studies on Tregs human autoimmunity have focused primarily peripheral blood samples. A study targeting diseased tissue should identify direct relationships between and Peripheral samples were collected from 91 patients with primary biliary cirrhosis (PBC), 28 immediate relatives, 41 healthy controls, Treg frequencies determined percentage of CD4+TCR-αβ+ cells. tissue-targeted...
Diabetic nephropathy is a major microvascular complication in long-standing diabetic patients who eventually undergo renal dialysis or transplantation. To prevent development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. In study, we examined whether inhibition receptor for glycation end products (RAGE) could attenuate changes kidney. Here, show that inactivation RAGE gene mouse model results significant...
Recently, we identified a child born with genetic deficiency of IL-2 receptor α (IL-2Rα, CD25) expression who had several clinical manifestations primary biliary cirrhosis (PBC). In addition, there has been suggestive evidence in both patients PBC and their first-degree relatives that regulatory T cells (Tregs) is an integral component for susceptibility to PBC. Based on these observations, generated IL-2Rα/CD25 deficient (IL-2Rα−/−) mice wild-type littermate controls followed them...
Recently the authors proposed a new staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity histological heterogeneity. Herein is convenient version of this system. Scores fibrosis, bile duct loss, chronic cholestasis were combined staging: stage 1, total score 0; 2, 1–3; 3, 4–6; 4, 7–9. Cholangitis (CA) hepatitis (HA) graded as CA0–3, HA0–3, respectively. Analysis interobserver agreement was then conducted. Digital images 62 needle...
Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays role in immune reactions recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, bioactive component of cell walls, and RAGE unclear. In this study, we found direct LPS binding by surface plasmon resonance assay, plate competition flow cytometry. increased TNF-α secretion from peritoneal macrophages an NF-κB...
The interleukin (IL)-12/IL-23-mediated Th1/Th17 signaling pathway has been associated with the etiopathogenesis of primary biliary cirrhosis (PBC). To address cytokine microenvironment specifically in liver, we examined localized expression subunits and their corresponding receptors using previously optimized immunohistochemistry an extensive panel antibodies directed at IL-12p70, IL-12p35, interferon-gamma (IFN-γ), IL-12RB2, IL-23p40, IL-23p19, IL-17, IL-23R liver from PBC (n = 51) non-PBC...
CXCL16 is a new member of the chemokine superfamily, which exists in transmembrane as well soluble form. Its receptor CXCR6 detected on CD4(+) T cells, CD8(+) and natural killer cells. Here, we report significant correlation expression by tumor cells with infiltration prognosis colorectal cancer (CRC). We first found that was consistently up-regulated more tissues than normal mucosa derived from same CRC patients. Four human cell lines also expressed mRNA secreted CXCL16. next examined...
There have been important advances in defining effector mechanisms for several human autoimmune diseases. However, most diseases, the induction stage is less well defined and there are very few clues on etiology. Our laboratory has focused molecular basis of autoantibody recognition epitope modification primary biliary cirrhosis (PBC). work demonstrated that antibodies to mitochondria, hallmark disease, directed against a conserved site pyruvate dehydrogenase, E2 subunit dehydrogenase...
Nonalcoholic fatty liver disease (NAFLD) is an abnormal metabolism often observed with insulin resistance and metabolic syndrome. Calorie restriction a useful treatment for NAFLD reportedly prolongs the life spans of several species in which sirtuin plays important role. In this study, we examined whether activation SIRT1, mammalian ortholog sirtuin, may ameliorate development NAFLD. Monosodium glutamate (MSG) mice, exhibited obesity resistance, were treated SRT1720, specific SIRT1 activator...
The chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancers and also shown participate the development of cancer metastasis. present study was carried out assess immunohistochemically pattern expression patients with metastatic prostate cancer. We analyzed whether there may an association between prognosis. Fifty‐two who received hormonal therapy were enrolled. Specimens obtained from transperineal needle biopsy before treatment, stained antihuman antibody....
The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for differentiation. Chemokines known to regulate cell migration adhesion. CX3CL1 (also called fractalkine) is a unique membrane-bound chemokine that has dual functions cells expressing its receptor CX3CR1: potent chemotactic factor in soluble form type efficient adhesion molecule form. In this paper, we demonstrate novel role osteoblast-induced We found selectively expressed...
Primary biliary cirrhosis (PBC) is characterized by chronic nonsuppurative destructive cholangitis (CNSDC) associated with destruction of small bile ducts. Although there have been significant advances in the dissection adaptive immune response against mitochondrial autoantigens, are increasing data that suggest a contribution innate mechanisms inducing pathology. We taken advantage our ability to isolate subpopulations liver mononuclear cells (LMC) and examined herein role Toll-like...
Cytokines play important roles in all stages of steatohepatitis, including hepatocyte injury, the inflammatory response, and altered function sinusoidal cells. This study examined involvement a major cytokine, interferon-γ (IFN-γ), progression steatohepatitis. In steatohepatitis model by feeding methionine- choline-deficient high-fat (MCDHF) diet to both wild-type IFN-γ-deficient mice, liver histology, expression genes encoding cytokines, fibrosis-related markers were examined. To analyze...
In most autoimmune diseases the serologic hallmarks of disease precede clinical pathology by years. Therefore, use animal models in defining early events becomes critical. We took advantage a "designer" mouse with dysregulation interferon gamma (IFNγ) characterized prolonged and chronic expression IFNγ through deletion 3'-untranslated region adenylate uridylate-rich element (ARE). The ARE-Del(-/-) mice develop primary biliary cholangitis (PBC) female predominance that mimics human PBC is...