A5102970196- Inflammatory mediators and NSAID effects
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Nitric Oxide and Endothelin Effects
- Immune Response and Inflammation
- Cancer Cells and Metastasis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Retinal Diseases and Treatments
- Tracheal and airway disorders
- Eicosanoids and Hypertension Pharmacology
- Mast cells and histamine
- Drug Transport and Resistance Mechanisms
- Airway Management and Intubation Techniques
- Chemokine receptors and signaling
- Dental Implant Techniques and Outcomes
- Urticaria and Related Conditions
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Trauma Management and Diagnosis
- Cancer, Stress, Anesthesia, and Immune Response
- S100 Proteins and Annexins
- Cancer Immunotherapy and Biomarkers
- Respiratory Support and Mechanisms
- Cancer Research and Treatments
The University of Tokyo
2013-2023
Nagasaki University
2022
Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how induces hyperpermeability focusing on the key regulators blood flow and endothelial barrier. Degranulation cells by antigen-stimulation or treatment induced tissue swelling mouse ears. These were abolished H1 receptor antagonism. Intravital imaging showed...
PGE2 is a major prostanoid that regulates inflammation by stimulating EP1-4 receptors. However, how induces an initial inflammatory response to vascular hyper-permeability remains unknown. Here we investigated the role of -EP receptor signal in modulating permeability both vivo and vitro.We used modified Miles assay intravital microscopy examine vivo. Endothelial barrier property was assessed measuring transendothelial electrical resistance (TER) vitro.Local administration , EP2 or EP4...
Abstract Thromboxane A 2 (TXA ) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution disease progression using three different ALI mouse models. The administration hydrochloric acid (HCl) or oleic (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA production experimental mice. LPS induced only accumulation without production. Pretreatment T prostanoid receptor (TP) antagonist attenuated but not these...
Abstract The effects of PGD2 are extremely context dependent. It can have pro- or anti-inflammatory in clinically important pathological conditions. A greater mechanistic insight into the determinants activity during inflammation is thus required. In this study, we investigated role croton oil–induced dermatitis using transgenic (TG) mice overexpressing hematopoietic PGD synthase. Administration oil caused tissue swelling and vascular leakage mouse ear. Compared with wild-type animals, TG...
Abstract Endothelial cells (ECs) are a key component of the tumor microenvironment. They have abnormal characteristics compared to ECs in normal tissues. Here, we found marked increase lipocalin‐type prostaglandin D synthase (L‐PGDS) mRNA ( Ptgds ) expression isolated from mouse melanoma. Immunostaining melanoma revealed L‐PGDS protein ECs. In situ hybridization also showed (PTGDS) human and oral squamous cell carcinoma. vitro experiments that stimulation with cell‐derived IL‐1 TNF‐α...
Although stromal cell-derived factor (SDF)-1αis well known to modulate the mobilization of hematopoietic stem cells and endothelial progenitor cells, its effects on some pre-existing vascular functions remain unknown. We have investigated here role SDF-1αsignaling in barrier function.Treatment with SDF-1α elevated transendothelial electrical resistance inhibited dextran hyperpermeability elicited by thrombin bovine aortic both indicating an increase function. binds 2 receptors, C-X-C...
Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, role prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption hematopoietic PGD synthase (H-PGDS) affects bleomycin-induced inflammation mouse. Compared H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition...
Bile acids are end products of cholesterol metabolism, and they constantly exist at high concentrations in the blood. Since vascular endothelial cells express G protein-coupled bile acid receptor (GPBAR), potentially modulate function. Here, we investigated whether how GPBAR agonism affects barrier In bovine aortic (BAECs), treatment with a agonist, taurolithocholic (TLCA) increased transendothelial electrical resistance. addition, TLCA suppressed thrombin-induced dextran infiltration...
Abstract Acute lung injury (ALI) is caused by various stimuli such as acid aspiration and infection, resulting in severe clinical outcomes with high mortality. Prostaglandin D 2 (PGD ) a lipid mediator produced the lungs of patients ALI. There are two prostaglandin synthases (PGDS), namely, lipocalin‐type PGDS (L‐PGDS) hematopoietic (H‐PGDS). We previously reported anti‐inflammatory role H‐PGDS‐derived PGD an endotoxin‐induced murine ALI model. Therefore, this study, we investigated...
In diabetic retinopathy (DR), pericyte dropout from capillary walls is believed to cause the breakdown of blood-retina barrier (BRB), which subsequently leads vision-threatening retinal edema. While various proinflammatory cytokines and chemokines are upregulated in eyes with DR, their distinct contributions disease progression remain elusive. Here, we evaluated roles stromal cell–derived factor-1α (SDF-1α) its receptor CXCR4 BRB initiated by deficiency. After inhibition recruitment...
Early diagnosis of colorectal cancer is needed to reduce the mortal consequence by cancer. Lipid mediators play critical role in progression colitis and colitis-associated colon (CAC) some their metabolites are excreted urine. Here, we attempted find novel biomarkers urinary lipid metabolite a murine model CAC. Mice were received single administration azoxymethane (AOM) repeated dextran sulfate sodium (DSS). urine was measured liquid chromatography mass spectrometry collected perform...
Normal angiogenesis is essential for retinal development and maintenance of visual function in the eye, its abnormality can cause retinopathy other eye diseases. Prostaglandin D2 an anti-angiogenic lipid mediator produced by lipocalin-type PGD synthase (L-PGDS) or hematopoietic (H-PGDS). However, exact role these synthases remains unclear. Therefore, we compared roles murine under physiological pathological conditions. On postnatal day (P) 8, WT retina was covered with elongated vessel....
Acute lung injury (ALI) is caused by various stimulates including aspiration of gastric contents. Although its mortality rate high, there no effective treatment against ALI. Prostaglandin D2 (PGD2) a bioactive substance which produced lipocalin-type PGD synthase (L-PGDS) and hematopoietic (H-PGDS). The production PGD2 increased in the patients with However, role remain unclear. Here we investigate L/H-PGDS-derived progression HCl-induced murine ALI model.
Although prostaglandin D2 (PGD2) represents anti-angiogenic role in tumor model, its physiological and pathological angiogenesis still remain unknown. We here evaluated the of PGD2 on retinal using genetically modified mice. In postnatal 8th day retina WT, lipocalin-type PGD synthase (L-PGDS) was expressed endothelial cells. Gene deficiency L-PGDS impaired retina, accompanied with increased mRNA expression pro-angiogenic factor VEGF. vitro study showed that inhibition elevated...
Abstract Osteosarcoma (OS) is characterized by TP53 mutations in humans. In mice, loss of p53 triggers OS development, and osteoprogenitor-specific -deleted mice are widely used to study the process osteosarcomagenesis. However, molecular mechanisms underlying initiation or progression following parallel inactivation remain largely unknown. Here, we examined role transcription factors involved adipogenesis (adipo-TFs) -deficient identified a novel tumor suppressive mechanism mediated C/ebpα....