title: Suppressive effect of β,β-dimethylacryloyl alkannin on activated dendritic cells in psoriasis by the TLR7/8 pathway.
abstract: β,β-dimethylacryloyl alkannin (DMA) is a key component of Lithospermum and possesses good efficacy for treating psoriasis. DMA inhibits activated dendritic cells (DCs), but the mechanism is unknown. Therefore, this study aimed to explore the modulation of the TLR7/8 pathway by DMA in psoriasis-activated DCs. Models of psoriasis-like skin lesions were established using BALB/c mice; 8 mice were treated with DMA (2.5mg/kg). Bone marrow cells were isolated and induced into DCs using R848, a TLR7/8 agonist. Splenic CD11c+ cells were detected by flow cytometry. Skin CD11c+ cells were detected by immunofluorescence. TLR7, TLR8, MYD88, and IRAKM proteins were detected by Western blot. The effects of DMA on surface molecules of DCs were observed by flow cytometry. mRNA expression of inflammatory factors was detected by qRT-PCR. Secreted cytokines were detected by cytometric bead array. Compared with the model group, psoriasis-like skin lesions were alleviated by DMA, the splenic CD11c+ cells were significantly decreased (P<0.01), and CD11c+ cell numbers in skin lesions were decreased (P<0.01). Expression levels of TLR7, MYD88, and IRAKM were significantly decreased (P<0.05). R848-stimulated DCs showed increased expression of I-A/I-E, CD80, and CD86 (P<0.01), increased IL-23 and IL-1β mRNA and secretion (P<0.05), and increased TLR7, TLR8, MYD88, and IRAKM expression (P<0.01); DMA inhibited all of these effects of the TLR7/8 pathway activation by R848 (P<0.05). In conclusion, DMA could inhibit psoriasis-activated DCs via the TLR7/8 pathway.
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Di
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Wang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Zhitong
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Xiangjiang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China. Electronic address: liping411@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D029684:Lithospermum; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy*; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D053583:Interleukin-1beta; D053759:Interleukin-23; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009285:Naphthoquinones; C552579:TLR8 protein, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C000617126:beta,beta-dimethylacryloyl alkannin; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse; C402365:resiquimod
keywords: Dendritic cells; Psoriasis; TLR7/8; β,β-dimethylacryloyl alkannin