title: Brazilin Limits Inflammatory Responses through Induction of Prosurvival Autophagy in Rheumatoid Fibroblast-Like Synoviocytes.
abstract: Brazilin is an active compound of Caesalpinia sappan L. (Leguminosae), which possesses pro-apoptotic and anti-inflammation potentials depending on the specific cell type. However, it is largely unknown whether autophagy is implicated in the mechanism underlying its chemotherapeutic and anti-inflammatory effects in rheumatoid arthritis (RA). Here, we show that treatment of RA fibroblast-like synoviocytes (FLS) with brazilin results in enhanced level of autophagic flux, evidenced by accumulation of autophagosome and increased level of lipidated LC3 (LC3-II), which is mainly mediated by enhanced production of reactive oxygen species (ROS). Interestingly, long-term exposure of brazilin was able to restore cell survival against the cytotoxity, exclusively in RA FLS, but not in normal fibroblast. Importantly, such a restoration from brazilin-induced cytotoxity in RA FLS was completely abrogated after co-treatment with autophagy inhibitors including NH4Cl or chloroquine. Furthermore, we found that the pretreatment of RA FLS with brazilin reduced LPS- or TNF-induced NF-κB activation and the secretion of inflammatory cytokines in parallel with the enhanced autophagic flux. Such anti-NF-κB potentials of brazilin were drastically masked in RA FLS when autophagy was suppressed. These results suggest that brazilin is capable of activating autophagy exclusively in RA FLS, and such inducible autophagy promotes cell survival and limits inflammatory response.
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Hyunji
authors: H
authors: Lee
authors: Division of Rheumatology, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Seong Wook
authors: SW
authors: Kang
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Hee Sun
authors: HS
authors: Byun
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Juhee
authors: J
authors: Jeon
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Kyeong Ah
authors: KA
authors: Park
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Kidong
authors: K
authors: Kang
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Wonhyoung
authors: W
authors: Seo
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Minho
authors: M
authors: Won
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Jeong Ho
authors: JH
authors: Seok
authors: Department of Biology, Soonchunhyang University, Asan, Chungnam, Republic of Korea.
authors: Man-Deuk
authors: MD
authors: Han
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors: Han-Ming
authors: HM
authors: Shen
authors: Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Gang Min
authors: GM
authors: Hur
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D041681:NIH 3T3 Cells; D017382:Reactive Oxygen Species / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C044362:brazilin