Anti-inflammatory effect of artemisinin on uric acid-induced NLRP3 inflammasome activation through blocking interaction between NLRP3 and NEK7
| Autor: | Seong-Kyu Kim, Jung-Yoon Choe, Ki-Yeun Park |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Lipopolysaccharide medicine.drug_class Inflammasomes Biophysics Anti-Inflammatory Agents Arthritis Inflammation Pharmacology Biochemistry Anti-inflammatory Cell Line 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cell Line Tumor parasitic diseases NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Humans NIMA-Related Kinases Artemisinin Molecular Biology integumentary system Macrophages Inflammasome Cell Biology medicine.disease Artemisinins Uric Acid Mice Inbred C57BL 030104 developmental biology chemistry 030220 oncology & carcinogenesis Uric acid medicine.symptom Intracellular medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 517(2) |
| ISSN: | 1090-2104 |
| Popis: | Objective Artemisinin is a potent anti-malarial agent that plays a potent role in regulating inflammatory disorders. NEK7 is a major interacting partner with NLRP3 in NLRP3 inflammasome. The aim of this study was to clarify the anti-inflammatory effect of artemisinin on activation of uric acid-induced NLRP3 inflammasome through regulation of NEK7. Methods Human macrophage U937 cells treated with lipopolysaccharide (LPS), monosodium urate (MSU) crystals, or artemisinin were used in in vitro study. Intracellular potassium (K+) level was measured in U937 cells treated with and without artemisinin. Expression of target genes or proteins NEK7, NLRP3, ASC, caspase-1, interleukin-1β (IL-1β), and NF-κB signaling molecules was measured. MSU crystal-induced arthritis model was used for in vivo study. Results Gout patients showed higher NLRP3 and NEK7 mRNA expression, compared to controls. Enhanced expression of NLRP3, caspase-1, and IL-1β was noted in macrophages treated with LPS (10 ng/ml) and MSU crystals (0.1 mg/ml), which was markedly suppressed by treatment with artemisinin (1, 10, and 100 μM). Artemisinin significantly inhibited interaction between NLRP3 and NEK7 in NLRP3 inflammasome activation. Artemisinin (10 and 100 μM) attenuated intracellular K+ efflux in macrophages stimulated with LPS and MSU crystals. Artemisinin suppressed foot and ankle swelling in MSU crystal-induced arthritis mice. Conclusion This study revealed that artemisinin inhibited activation of NLRP3 inflammasome by suppressing interaction between NEK7 and NLRP3 in uric acid-induced inflammation. |
| Databáze: | OpenAIRE |
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