title: Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone erosion. Fibroblast-like synoviocytes (FLS) play a pivotal role in RA pathogenesis through aggressive migration and matrix invasion, and certain proinflammatory cytokines may affect synoviocyte invasion. Whether interleukin (IL)-21 influences this process remains controversial. Here, we evaluated the potential regulatory effect of IL-21 on the migration, invasion and matrix metalloproteinase (MMP) expression in RA-FLS. We found that IL-21 promoted the migration, invasion and MMP (MMP-2, MMP-3, MMP-9, MMP-13) production in RA-FLS. Moreover, IL-21 induced activation of the phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways, and blockage of these pathways [PI3K/protein kinase B (AKT) inhibitor LY294002, STAT-3 inhibitor STA-21 and ERK1/2 inhibitor PD98059] attenuated IL-21-induced migration and secretion of MMP-3 and MMP-9. In conclusion, our results suggest that IL-21 promotes migration and invasion of RA-FLS. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Xing
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015820:Cadherins / Q000096:biosynthesis; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011083:Polycyclic Compounds / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D015820:Cadherins; D002867:Chromones; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D018799:Intercellular Adhesion Molecule-1; D007378:Interleukins; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011083:Polycyclic Compounds; D050796:STAT3 Transcription Factor; D000098546:Interleukin-21; C573420:ICAM1 protein, human; C500947:STA-21; C494086:STAT3 protein, human; C086960:osteoblast cadherin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C507079:MMP13 protein, human; C511768:MMP3 protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: fibroblast-like synoviocytes; interleukin-21; invasion; matrix metalloproteinases; migration