title: Indirubin inhibits the migration, invasion, and activation of fibroblast-like synoviocytes from rheumatoid arthritis patients.
abstract: OBJECTIVE
  To evaluate the inhibition of indirubin in FLSs migration, invasion, activation, and proliferation in RA FLSs.
  
  
  METHODS
  The levels of IL-6 and IL-8 in cultural supernatants were measured by ELISA. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction protein expression was measured by western blot. FLS proliferation was detected by Edu incorporation. F-actin was measured by immunofluorescence staining.
  
  
  RESULTS
  We found that indirubin reduced migration, invasion, inflammation, and proliferation in RA FLSs. In addition, we demonstrated that indirubin inhibited lamellipodium formation during cell migration. To gain insight into molecular mechanisms, we evaluated the effect of indirubin on PAK1 and MAPK activation. Our results indicated that indirubin inhibited the activity of PAK1 and MAPK.
  
  
  CONCLUSIONS
  Our observations suggest that indirubin may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, activation, and proliferation.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
authors.forename: Mingcheng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The People's Hospital of Nanhai District, Foshan, Guangdong, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China. lliuq@mail.sysu.edu.cn.
authors.forename: Liuqin
authors.initials: L
authors.lastname: Liang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000070918:Synoviocytes / Q000187:drug effects* / Q000502:physiology; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007211:Indoles; D012333:RNA, Messenger; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D020928:Mitogen-Activated Protein Kinases; C027185:indirubin
keywords: Fibroblast-like synoviocytes; Indirubin; Inflammation; MAPK; Migration; PAK1