Cyclic phosphatidic acid (cPA) is a lipid mediator, which regulates adipogenic differentiation and glucose homeostasis by suppressing nuclear peroxisome proliferator-activated receptor γ (PPARγ). Glycerophosphodiesterase 7 (GDE7) Ca2+-dependent lysophospholipase D that localizes in the endoplasmic reticulum. Although mouse GDE7 catalyzes cPA production cell-free system, it unknown whether generates living cells. Here, we demonstrate human possesses cPA-producing activity cells as well...

Although subtle barrier defects may facilitate allergen penetration, thereby enabling allergic sensitization, the relationship between sweating disturbance and skin function is unknown. However, many studies on contact hypersensitivity in mice examined ear skin, which does not sweat, instead of footpad, where uniquely present. In this study, we assessed whether sweat suppression footpad before hapten application provoked a abnormality reduced inflammatory thresholds to topical haptens. Mice...

Abstract This study investigated effects of a fluoxetine (selective serotonin reuptake inhibitors; SSRI, 1 mg/kg) on pruritus in canine atopic dermatitis (CAD). After 4-weeks base-line observation, 8 dogs with CAD entered 2-months randomized, double-blind, placebo-controlled, crossover trial comparing placebo. Clinical efficacy was evaluated using Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) Pruritus Visual Analog Scale (PVAS). Six completed the [two out eight (both them...

Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets current antifibrotic drugs, no drug has yet been approved stop fibrosis progression. Herein, we aimed identify GPCRs with profibrotic effects. In gene expression analysis mouse lungs induced fibrosis, eight were identified, showing a >2-fold increase mRNA after...

Abstract Twenty dogs with canine atopic dermatitis (CAD) were treated rush sublingual immunotherapy (SLIT), a 48 hour build-up phase and 6 months maintenance (treated by antigen once every 3-4 weeks). The extent severity index (CADESI)-4 was evaluated before treatment (baseline) after months. An open, non-controlled, non-randomized pilot trial conducted to assess the effectiveness safety of SLIT for environmental allergen extracts (Dematophagoides pteronyssinus D.farinae mix other). Three...

Abstract In this study, dogs were separated into two groups and treated with immunosuppressant (Cyclosporin A: CsA). The first group was the canine atopic dermatitis (CAD) group, which is similar to extrinsic (AD) in humans (treated a CsA dose of 2.5-5.5 mg/kg, n=8), second atopic-like (ALD) intrinsic AD 2.5-6.5 n=14). extent severity index (CADESI)-4 evaluated before treatment (PRE) after (POST) assess effectiveness for groups. CAD CADESI-4 showed no change (PRE:79±29, POST:77±28) out eight...

Lysophosphatidic acid (LPA) is a lipid mediator that regulates various processes, including cell migration and cancer progression. Autotaxin (ATX) lysophospholipase D-type exoenzyme produces extracellular LPA. In contrast, glycerophosphodiesterase (GDE) family members GDE4 GDE7 are intracellular lysophospholipases D form LPA, depending on Mg2+ Ca2+, respectively. Since no fluorescent substrate for these GDEs has been reported, in the present study, we examined whether ATX substrate, FS-3,...

This study investigated the influence of 0.00584% hydrocortisone aceponate spray (HCA; Cortavance Virbac SA, Carros, France) on blood serum cortisol levels and peripheral CCR4(+) CD4(+) T-lymphocyte in dogs with atopic dermatitis. Patients were randomly divided into group I (N = 8) II 8). The sprayed HCA affected skin once a day for three weeks. treated 3 days followed by no treatment 4 total For CADESI-03 scores before after use showed significant reduction (P < 0.01). postcortisol level...

We reported that sphingosine 1-phosphate type2 receptor (S1P2)/Rho kinase pathway is necessary for full activation of STAT6 by IL-4/IL-13 in phorbol ester-treated THP-1 macrophages (MΦs) at the 94th Annual Meeting Japanese Pharmacological Society. This time, we report further results. The S1P2knockout MΦs showed lower activities phosphorylation response to IL-4 or IL-13 stimulation than wild-type MΦs. decrease IL-4-induced was prevented ectopic expression mouse S1pr2. S1P2 regulates Rho/Rho...

Lysophosphatidic acid (LPA) is a lipid mediator which regulates various biological processes, including cell proliferation, platelet aggregation, and cancer metastasis. Autotaxin (ATX) lysophospholipase D (lyso-PLD)-type enzyme that produces LPA in plasma. In contrast, glycerophosphodiesterase GDE4 GDE7 (GDEs) are intracellular lyso-PLDs producing LPA. ATX GDEs may play unique roles, need to be validated with their potent selective inhibitors. Although fluorescent substrates useful for...

The involvement of senescent cells in the lungs idiopathic pulmonary fibrosis has been strongly suggested. In our previous study, we confirmed cellular senescence macrophages and expression p16INK4a, a key marker senescence, from bleomycin-induced model mice. However, role macrophage not clarified. present investigated lung using macrophage-specific p16 knockout (p16 cKO) While bleomycin treatment increased mRNA whole tissue control mice, such an effect was observed cKO We also examined...

Abstract Cyclic phosphatidic acid (cPA) is a lipid mediator, which regulates adipogenesis and glucose homeostasis by suppressing nuclear peroxisome proliferator-activated receptor γ (PPARγ). Glycerophosphodiesterase 7 (GDE7) Ca 2+ -dependent lysophospholipase D that localizes in the endoplasmic reticulum. Although mouse GDE7 catalyzes cPA production cell-free system, it unknown whether generates living cells. Here, we demonstrate human possesses cPA-producing activity cells as well system....

Senescent cells are strongly implicated in various diseases including idiopathic pulmonary fibrosis. In our previous study, we confirmed expression of p16, a key marker cellular senescence, the alveolar epithelial (AECs) lungs from bleomycin-induced fibrosis model mice. Although AECs have been reported to contribute lung through epithelial-mesenchymal transition (EMT), it remains unclear whether induction EMT is influenced by AEC senescence. present investigated roles senescence using...

Cyclic phosphatidic acid (cPA) is a lipid mediator present in tissues and plasma, which regulates physiological pathological processes via the suppression of peroxisome proliferator-activated receptor γ (PPARγ). Glycerophosphodiesterase 7 (GDE7) an endoplasmic reticulum-localized lysophospholipase D-type enzyme, mouse GDE7 was reported to catalyze production cPA cell-free systems. However, it remains unknown whether this reaction occurs living cells. In study, we found that overexpression...