title: Shikonin inhibits TNF-α production through suppressing PKC-NF-κB-dependent decrease of IL-10 in rheumatoid arthritis-like cell model.
abstract: Shikonin, a major effective component in the Chinese herbal medicine Lithospermum erythrorhizon Sieb., exhibits an anti-inflammatory property towards rheumatoid arthritis (RA), but the potential mechanism is unclear. Our aim was to investigate the mechanism of shikonin on the lipopolysaccharide (LPS)-induced fibroblast-like synoviocyte (LiFLS) inflammation model. Fibroblast-like synoviocytes (FLSs) were treated with 200 μg/ml of LPS for 24 h to establish the RA-like model, LiFLS. FLSs were pretreated with shikonin (0.1-1 μM) for 30 min in the treatment groups. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect mRNA and protein levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α. Signal proteins involved in IL-10 production were analyzed by Western blotting. Shikonin significantly reversed the inhibitory effects of LPS on IL-10 expression in FLSs by inactivating the PKC-NF-κB pathway. In addition, shikonin inhibited LPS-induced TNF-α expression in FLSs, and this effect was markedly diminished by IL-10-neutralizing antibody. The IL-10-mediated suppression of TNF-α transcription was demonstrated by no response to the protein synthesis inhibitor cyclohexamide and no mRNA decay. Shikonin inhibits LPS-induced TNF-α production in FLSs through suppressing the PKC-NF-κB-dependent decrease in IL-10, and this study also highlights the potential application of shikonin in the treatment of RA.
authors.affiliation: Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430077, Hubei, China.
authors.forename: Wen-Xiao
authors.initials: WX
authors.lastname: Sun
authors.affiliation: Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430077, Hubei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430077, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430077, Hubei, China.
authors.forename: He-Wei
authors.initials: HW
authors.lastname: Li
authors.affiliation: Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430077, Hubei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopedic and Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China. sunwenxiao2014@126.com.
authors.forename: Zhen-Bing
authors.initials: ZB
authors.lastname: Chen
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009285:Naphthoquinones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D009285:Naphthoquinones; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C016101:shikonin
keywords: Inflammation; Lithospermum erythrorhizon; Protein kinase C; Protein synthesis; Rheumatoid arthritis; mRNA stability