title: A novel small molecule compound possesses immunomodulatory properties on bone marrow-derived dendritic cells via TLR7 signaling pathway and alleviates the development of SLE.
abstract: Dendritic cells (DCs) play an important role in the development and maintenance of immune tolerance. Activation of TLR7, which is expressed in DCs, is thought to contribute to the complex pathophysiology of systemic lupus erythematosus (SLE). In this study, we analyzed the in vitro and in vivo function of a novel small-molecule compound, FC-99, which was previously reported to have immunomodulatory functions. We found that FC-99 inhibited the expression of CD40 and inflammatory mediators (IL-6, IL-12, and CXCL-10), as well as R848-induced phosphorylation of IκB-α. We also present evidence that FC-99 is remarkably efficacious in the treatment of murine lupus. Interestingly, FC-99 affected the maturation and percentage of DCs in lupus-prone mice. Therefore, FC-99 may serve as a potential drug candidate for treatment of SLE.
authors.affiliation: Laboratory Animal Center, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Orthopedics, The Third People's Hospital of Linyi, Linyi 276000, Shandong Province, China.
authors.forename: Cunyu
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Han
authors.affiliation: School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China. Electronic address: huachunyan@wmu.edu.cn.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hua
mesh_terms: D000476:Alkanesulfonates / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000502:physiology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005466:Fluorocarbons / Q000627:therapeutic use*; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D000476:Alkanesulfonates; D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D005466:Fluorocarbons; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; C051585:Fluorad FC99
keywords: DCs; FC-99; SLE; TLR7