title: Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid.
abstract: Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA) was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS)-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO) and prostaglandin (PG) E₂ from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF)-κB and activator protein (AP)-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1) and spleen tyrosine kinase (Syk). Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea. wannabejk@naver.com.
authors.forename: Jae Gwang
authors.initials: JG
authors.lastname: Park
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon 57922, Korea. sony@sunchon.ac.kr.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.affiliation: School of Systems Biomedical Science, Soongsil University, Seoul 06978, Korea. kimmy@ssu.ac.kr.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea. jaecho@skku.edu.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000880:Anthraquinones / Q000008:administration & dosage* / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D001938:Brazil; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009569:Nitric Oxide / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D000072377:Syk Kinase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D029663:Tabebuia / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011453:Prostaglandins; D018808:Transcription Factor AP-1; C498247:anthraquinone-2-carboxylic acid; D009569:Nitric Oxide; D000072377:Syk Kinase; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: IRAK1; anthraquinone-2-carboxylic acid; anthraquinones; inflammatory response