title: Visfatin/pre-B-cell colony-enhancing factor (PBEF), a proinflammatory and cell motility-changing factor in rheumatoid arthritis.
abstract: Adipokines such as adiponectin and visfatin/pre-B-cell colony-enhancing factor (PBEF) have been recently shown to contribute to synovial inflammation in rheumatoid arthritis (RA). In this study, we evaluated the pathophysiological implication of visfatin/PBEF in the molecular patterns of RA synovial tissue, focusing on RA synovial fibroblasts (RASFs), key players in RA synovium. Expression of visfatin/PBEF in synovial fluid and tissue of RA patients was detected by immunoassays and immunohistochemistry. RASFs were stimulated with different concentrations of visfatin/PBEF over varying time intervals, and changes in gene expression were evaluated at the RNA and protein levels using Affymetrix array, real-time PCR, and immunoassays. The signaling pathways involved were identified. The influence of visfatin/PBEF on fibroblast motility and migration was analyzed. In RA synovium, visfatin/PBEF was predominantly expressed in the lining layer, lymphoid aggregates, and interstitial vessels. In RASFs, visfatin/PBEF induced high amounts of chemokines such as IL-8 and MCP-1, proinflammatory cytokines such as IL-6, and matrix metalloproteinases such as MMP-3. Phosphorylation of p38 MAPK was observed after visfatin/PBEF stimulation, and inhibition of p38 MAPK showed strong reduction of visfatin-induced effects. Directed as well as general fibroblast motility was increased by visfatin/PBEF-induced factors. The results of this study indicate that visfatin/PBEF is involved in synovial fibroblast activation by triggering fibroblast motility and promoting cytokine synthesis at central sites in RA synovium.
authors: Department of Internal Medicine and Rheumatology, Justus-Liebig University Giessen, and the Kerckhoff Klinik, D-61231 Bad Nauheim, Germany.
authors: Florian M P
authors: FM
authors: Meier
authors: Klaus W
authors: KW
authors: Frommer
authors: Marvin A
authors: MA
authors: Peters
authors: Fabia
authors: F
authors: Brentano
authors: Stephanie
authors: S
authors: Lefèvre
authors: Dirk
authors: D
authors: Schröder
authors: Diego
authors: D
authors: Kyburz
authors: Jürgen
authors: J
authors: Steinmeyer
authors: Stefan
authors: S
authors: Rehart
authors: Steffen
authors: S
authors: Gay
authors: Ulf
authors: U
authors: Müller-Ladner
authors: Elena
authors: E
authors: Neumann
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D054409:Nicotinamide Phosphoribosyltransferase / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D048051:p38 Mitogen-Activated Protein Kinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3