Novel Piperazino-Enaminones Decrease Pro-inflammatory Cytokines Following Hemarthrosis in a Hemophilia Mouse Model
| Autor: | Doreen E. Szollosi, Junjiang Sun, Baolai Hua, Ivan O. Edafiogho, Ashley Bill, Chen Zhong, Yingping Zhuang, Ola Ghoneim |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Chemokine medicine.medical_treatment Immunology Inflammation Hemophilia A Proinflammatory cytokine Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine In vivo Hemarthrosis Arthropathy medicine Animals Immunology and Allergy Piperazine Neovascularization Pathologic biology business.industry Ketones medicine.disease Disease Models Animal 030104 developmental biology Cytokine 030220 oncology & carcinogenesis biology.protein Cytokines medicine.symptom business |
| Zdroj: | Inflammation. 42:1719-1729 |
| ISSN: | 1573-2576 0360-3997 |
| Popis: | Hemarthrosis is the primary cause of hemophiliac arthropathy (HA). Pro-inflammatory cytokines are thought to play an important role in the pathogenesis of HA, and thus, anti-cytokine approaches may be used as an adjuvant therapy. A novel series of enaminone compounds (JODI), that contain the N-aryl piperazino motif, have been shown in vitro to reduce pro-inflammatory cytokines and thus may be efficacious in vivo. In this report, we will assess whether JODI can suppress multiple cytokines which might be potentially responsible for joint inflammation in a mouse model of hemarthrosis. The results showed that JODI significantly improved the survival after LPS treatment, and most pro-inflammatory cytokines/chemokines were decreased significantly after JODI administration. In the hemophilia mouse model, hemarthrosis resulted in local cytokine/chemokine changes, represented by elevated pro-inflammatory (IL-6, MCP-1, MIP-1α, MIP-1β) and pro-angiogenic (VEGF and IL-33) cytokines, and decreased anti-pro-inflammatory cytokines IL-4 and IL-10. The changes were reversed by administration of JODI, which can be used as a novel approach to manage hemophilia arthropathy. |
| Databáze: | OpenAIRE |
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