200-LB: Ceramide Kinase CERK Regulates Inflammatory Responses in Monocytes/Macrophages Induced by TNF-a
| Autor: | Rasheed Ahmad, Fatema Al-Rashed |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Ceramide
biology Chemistry Endocrinology Diabetes and Metabolism p38 mitogen-activated protein kinases CD11c Inflammation Proinflammatory cytokine Cell biology chemistry.chemical_compound Integrin alpha M Ceramide kinase Internal Medicine medicine biology.protein Tumor necrosis factor alpha medicine.symptom |
| Zdroj: | Diabetes. 69 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db20-200-lb |
| Popis: | Obesity is associated with elevated levels of TNF-α and proinflammatory CD11c monocytes/macrophages. TNF-α mediated dysregulation in the plasticity of monocytes/macrophages is concomitant with pathogenesis of several inflammatory diseases, including metabolic syndrome, but the underlying mechanisms are incompletely understood. Since Ceramide kinase (CERK; a critical mediator of eicosanoid synthesis, and its product, ceramide-1-phosphate (C1P)) is a key enzyme for ceramide production involved in inflammation, we investigated whether the CERK contributed to the inflammatory changes in the monocytes/macrophages induced by TNF-α. In this study, we demonstrate that the disruption of CERK activity in monocytes/macrophages either by chemical inhibitor NVP- 231 or small interfering RNA (siRNA)against CERK gene results in defects in the TNF-α mediated expression of CD11c and CD11b and HLA-Dr. Furthermore, blockage of CERK in monocytes/macrophages inhibited the secretion of IL-1b and MCP-1. Phosphorylation of JNK, p38 and NF-κB resulting from TNF-α stimulation was also attenuated by the inhibition of CERK. Moreover, NF-kB/AP-1 activity was blocked by the inhibition of CERK. Our human data show that CERK was elevated in PBMCs from obese individuals and positively corelated with TNF-α. These findings indicate that CERK acts, in a part, as a master switch in the TNF-α mediated inflammatory responses in monocytes/macrophages. Disclosure F. Alrashed: None. R. Ahmad: None. Funding Kuwait Foundation for the Advancement of Sciences (RA-AM 2016007) |
| Databáze: | OpenAIRE |
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