Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling
| Autor: | Sushil K. Mahata, Ramon L. Serrano, Ru Liu-Bryan, Charles McWherter, Robert Terkeltaub, Yun-Jung Choi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
AMPK lcsh:Diseases of the musculoskeletal system Gout Mitochondrion AMP-Activated Protein Kinases medicine.disease_cause Inbred C57BL Mice AMP-activated protein kinase Acetamides 2.1 Biological and endogenous factors Autophagy flux Aetiology Receptor Cells Cultured Phenylacetates Cultured biology Chemistry 3. Good health Mitochondria 5.1 Pharmaceuticals Public Health and Health Services Phosphorylation Inflammation Mediators Development of treatments and therapeutic interventions Research Article Signal Transduction Cells Clinical Sciences Immunology Bone Marrow Cells 03 medical and health sciences medicine Animals Protein kinase A Inflammation Arthritis Inflammatory and immune system Autophagy Molecular biology Uric Acid Arthritis & Rheumatology Mice Inbred C57BL 030104 developmental biology biology.protein lcsh:RC925-935 Oxidative stress |
| Zdroj: | Arthritis research & therapy, vol 20, iss 1 Arthritis Research & Therapy Arthritis Research & Therapy, Vol 20, Iss 1, Pp 1-11 (2018) |
| Popis: | Background Arhalofenate acid, the active acid form of arhalofenate, is a non-agonist peroxisome proliferator-activated receptor γ (PPARγ) ligand, with uricosuric activity via URAT1 inhibition. Phase II studies revealed decreased acute arthritis flares in arhalofenate-treated gout compared with allopurinol alone. Hence, we investigated the anti-inflammatory effects and mechanisms of arhalofenate and its active acid form for responses to monosodium urate (MSU) crystals. Methods We assessed in-vivo responses to MSU crystals in murine subcutaneous air pouches and in-vitro responses in murine bone marrow-derived macrophages (BMDMs) by enzyme-linked immunosorbent assay (ELISA), SDS-PAGE/Western blot, immunostaining, and transmission electron microscopy analyses. Results Oral administration of arhalofenate (250 mg/kg) blunted total leukocyte ingress, neutrophil influx, and air pouch fluid interleukin (IL)-1β, IL-6, and CXCL1 in response to MSU crystal injection (p |
| Databáze: | OpenAIRE |
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