title: (5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lprmice by preventing infiltration of immune cells.
abstract: (5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative with low toxicity, was previously reported to have strong immunosuppressive effects both in vitro and in vivo, but it remains unknown whether LLDT-8 has a therapy effect on systemic lupus erythematosus. In this study, we aimed to investigate the therapeutic effects of LLDT-8 on lupus nephritis in MRL/lprmice, a model of systemic lupus erythematosus. Compared with the vehicle group, different clinical parameters were improved upon LLDT-8 treatment as follows: prolonged life span of mice, decreased proteinuria, downregulated blood urea nitrogen and serum creatinine, reduced glomerular IgG deposits, and ameliorated histopathology. A decreased expression of the inflammatory cytokines IFN-γ, IL-17, IL-6, and TNF-α was also observed in the kidney of LLDT-8 treated MRL/lprmice. Moreover, infiltration of T cells in the kidney was mitigated after LLDT-8 treatment, corresponding with decreased expression of related chemokines IP-10, Mig, and RANTES in the kidney. The proportion of macrophage and neutrophil cells and related chemokines expression was also reduced in kidneys of LLDT-8-treated mice. In the human proximal tubule epithelial cell line and mouse mesangial cell line, consistent with our in vivo experimental results, LLDT-8 suppressed the expression of related chemokines and IL-6. In summary, LLDT-8 has a therapeutic benefit for lupus nephritis via suppressing chemokine expression and inhibiting immune cell infiltration in kidneys of MRL/lprmice.
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lu-Yao
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yu-Xi
authors.initials: YX
authors.lastname: Yan
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Yang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Zhu
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: He
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; and jpzuo@simm.ac.cn.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D002460:Cell Line; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019463:Mice, Inbred MRL lpr; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011507:Proteinuria / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: C509074:5-hydroxytriptolide; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D004224:Diterpenes; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D003404:Creatinine
keywords: chemokines; inflammation; systemic lupus erythematosus