Resolvin D2 suppresses NLRP3 inflammasome by promoting autophagy in macrophages
| Autor: | Lixiu Liu, Zhen Li, Feijuan Lv, Yiya Wang, Yina Wang, Lijun Cao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
NLR family pyrin domain containing 3 Chemistry Autophagy Pyroptosis Inflammation Inflammasome Articles macrophage General Medicine Pyrin domain Cell biology AIM2 Immunology and Microbiology (miscellaneous) inflammasome inflammation NLRC4 medicine CARD domain resolvin D2 medicine.symptom medicine.drug |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| Popis: | Inflammasome, a multiprotein complex that regulates interleukin (IL)-1β secretion and pyroptosis, participates in numerous inflammatory diseases, including sepsis, atherosclerosis and type-2 diabetes. Investigating the inflammasome regulation is therefore crucial to understand the inflammasome activation and develop treatment for the related diseases. In addition, it remains unknown how the inflammasome is naturally suppressed during the inflammatory process. The present study aimed to investigate the role of resolvin D2 (RvD2), an innate suppressor of inflammation produced from essential ω3-polyunsaturated fatty acids, in the activation of the inflammasome via in vitro and in vivo experiments. The effects of RvD2 on the cytokine production of inflammasome-related peritonitis were determined, and the NLRP3 inflammasome activation was investigated in the presence of RvD2. Moreover, the potential mechanisms underlying RvD2 in NLRP3 inflammasome regulation through autophagy and proteasome were investigated. The results of the present study demonstrated that RvD2 suppressed inflammasome-mediated peritonitis in vivo and regulated the NLR family pyrin domain containing 3 (NLRP3) inflammasome, but not in absent in melanoma 2 (AIM2), NLR family CARD domain containing 4 (NLRC4) inflammasomes. Mechanistically, RvD2 was found to promote the degradation of NLRP3 through autophagy, and the inhibition of autophagy could reverse the RvD2-mediated suppression of NLRP3 inflammasome in vitro and partially reverse the inflammasome-mediated peritonitis in vivo. In summary, the present study reported the negative regulation of NLRP3 inflammasome activation by RvD2. The findings from this study may extend the knowledge of the innate regulation of inflammasome and highlight a possible target for inflammasome-related diseases. |
| Databáze: | OpenAIRE |
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