title: Interleukin-35 upregulates OPG and inhibits RANKL in mice with collagen-induced arthritis and fibroblast-like synoviocytes.
abstract: IL-35 is a novel anti-inflammatory cytokine, but the exact role of IL-35 in the progression of RA remains unclear, especially associated with osteoporosis and bone erosion. The present research has not been reported. Our purpose is to study how IL-35 affects RA bone destruction.
  
  
  BACKGROUND
  This study investigated the effect of interleukin-35 (IL-35) on OPG and RANKL expression in collagen-induced arthritis (CIA) in rats and in cultured fibroblast-like synoviocytes (FLS).
  
  
  METHODS
  Thirty DBA/1J mice were randomly assigned to three groups (n = 10 per group): the control group, the CIA group, and the CIA + IL-35 group. Collagen-induced arthritis was induced by immunization with collagen. IL-35 was intraperitoneally injected daily for 10 days, starting from the 24(th) day after immunization. FLS cells were isolated and cultured from CIA. The expression of IL-17, RANKL, and OPG was determined by RT-PCR and Western blot. Each experiment was repeated three times.
  
  
  RESULTS
  CIA mice exhibited arthritis symptoms on day 24, followed by a rapid progression of arthritis. The expression of IL-17 and RANKL was increased and the expression of OPG was decreased in CIA mice compared with control mice. IL-35 treatment inhibited the development of arthritis in CIA mice, accompanied by a decrease in the expression of IL-17 and RANKL and an increase in the expression of OPG. Furthermore, IL-35 dose-dependently inhibited the expression of RANKL and increased the expression of OPG in cultured FLS cells.
  
  
  CONCLUSIONS
  IL-35 inhibits RANKL expression and increases OPG expression in CIA mice. IL-35 may be used for treating rheumatoid arthritis.
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, People's Republic of China. lujingtan@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000517:prevention & control; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D007378:Interleukins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008811:Mice, Inbred DBA; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D000070918:Synoviocytes / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; C569375:interleukin-35, mouse
keywords: Interleukin-35; OPG; RANKL; Rheumatic arthritis