PMID- 29686531 OWN - NLM STAT- MEDLINE DCOM- 20180917 LR - 20181114 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2018 DP - 2018 TI - Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation. PG - 6054069 LID - 10.1155/2018/6054069 [doi] LID - 6054069 AB - Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1beta regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1beta levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis. FAU - Kwak, Su-Bin AU - Kwak SB AD - Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea. FAU - Koppula, Sushruta AU - Koppula S AD - Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea. FAU - In, Eun-Jung AU - In EJ AD - Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea. FAU - Sun, Xiao AU - Sun X AD - Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea. FAU - Kim, Young-Kyu AU - Kim YK AD - Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea. FAU - Kim, Myong-Ki AU - Kim MK AUID- ORCID: 0000-0002-2956-7006 AD - Department of Food Science and Engineering, Seowon University, Cheongju, Republic of Korea. FAU - Lee, Kwang-Ho AU - Lee KH AUID- ORCID: 0000-0002-3677-0977 AD - Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea. AD - Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, 268 Chungwon-daero, Chungju, Republic of Korea. FAU - Kang, Tae-Bong AU - Kang TB AUID- ORCID: 0000-0003-1441-9470 AD - Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea. AD - Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, 268 Chungwon-daero, Chungju, Republic of Korea. LA - eng PT - Journal Article DEP - 20180304 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Aim2 protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Plant Extracts) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Artemisia/*chemistry MH - Cells, Cultured MH - DNA-Binding Proteins/genetics/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Fluorescent Antibody Technique MH - Inflammasomes/*drug effects/*metabolism MH - Interleukin-1beta/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism MH - Phosphorylation/drug effects MH - Plant Extracts/chemistry/*therapeutic use MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC5857320 EDAT- 2018/04/25 06:00 MHDA- 2018/09/18 06:00 PMCR- 2018/03/04 CRDT- 2018/04/25 06:00 PHST- 2017/06/30 00:00 [received] PHST- 2017/12/14 00:00 [revised] PHST- 2018/01/03 00:00 [accepted] PHST- 2018/04/25 06:00 [entrez] PHST- 2018/04/25 06:00 [pubmed] PHST- 2018/09/18 06:00 [medline] PHST- 2018/03/04 00:00 [pmc-release] AID - 10.1155/2018/6054069 [doi] PST - epublish SO - Mediators Inflamm. 2018 Mar 4;2018:6054069. doi: 10.1155/2018/6054069. eCollection 2018.