The Role of 15-Lipoxygenase on NLRP3 Inflammasome Activation
| Autor: | Yueh-Tung Lu, 陸玥彤 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 The NLRP3 inflammasome, a reactive oxygen species-sensitive multiprotein complex, regulates IL-1 maturation via caspase-1 and plays an important role in the pathogenesis of inflammation-related disease. LOX catalyzes the oxidation of fatty acids and is involved in the regulation of the innate and adaptive immune response. However, the role of LOX on NLRP3 inflammasome activation is unclear. In this study we found that NLRP3 inflammasome-derived IL-1 secretion was reduced by inhibitor of 15-LOX, but not by inhibitor of 5-LOX and 12-LOX. The effect of 15-LOX on NLRP3 inflammasome was further confirmed by genetic knockdown of 15-LOX by shRNA. The underlying mechanisms for the 15-LOX-mediated increase in NLRP3 inflammasome activation were (1) enhancement of the expression levels of proIL-1 and NLRP3 by increasing NF-B activation and phosphorylation of JNK1/2, PKC-α/, whereas phosphorylation of ERK1/2 and p38 were decreased; (2) enhancement of the caspase-1 activation by increasing damaged mitochondria, mitochondrial ROS generation, and mitochondrial DNA release into cytosol; (3) enhancement of the expression levels of proIL-1 and NLRP3 and caspase-1 activation by reducing autophagy. In summary, 15-LOX positive regulates the NLRP3 inflammasome activation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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