title: 6-Mer hyaluronan oligosaccharides increase IL-18 and IL-33 production in mouse synovial fibroblasts subjected to collagen-induced arthritis.
abstract: Hyaluronan (HA) oligosaccharides stimulate pro-inflammatory responses in different cell types by modulating both cluster determinant 44 (CD44) and TLR4. The activation of these receptors is also mediated by collagen-induced arthritis (CIA) that, via two different pathways, culminates in the liberation of NF-κB. This then stimulates the production of pro-inflammatory cytokines, including IL-18 and IL-33, that are greatly involved in rheumatoid arthritis. The aim of this study was to investigate the effects of 6-mer HA oligosaccharides on mouse synovial fibroblasts obtained from normal DBA/J1 mice or mice subjected to CIA. Compared with normal synovial fibroblasts (NSF), rheumatoid arthritis synovial fibroblasts (RASF) showed no up-regulation of CD44 and TLR4 mRNA expression and the related proteins, as well as no activation of NF-κB. Very low levels of both mRNA and related proteins were also detected for IL-18 and IL-33. Treatment of NSF and RASF with 6-mer HA oligosaccharides significantly increased all the parameters in both fibroblast groups, although to a greater extent in RASF. The addition of hyaluronan binding protein to both NSF and RASF inhibited HA activity and was able to reduce the effects of 6-mer HA oligosaccharides and the consequent inflammatory response.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, School of Medicine, University of Messina, Policlinico Universitario, Messina, Italy. gcampo@unime.it
authors.forename: Giuseppe M
authors.initials: GM
authors.lastname: Campo
authors.forename: Angela
authors.initials: A
authors.lastname: Avenoso
authors.forename: Angela
authors.initials: A
authors.lastname: D'Ascola
authors.forename: Michele
authors.initials: M
authors.lastname: Scuruchi
authors.forename: Vera
authors.initials: V
authors.lastname: Prestipino
authors.forename: Alberto
authors.initials: A
authors.lastname: Calatroni
authors.forename: Salvatore
authors.initials: S
authors.lastname: Campo
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology*; D013583:Synovial Membrane / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D018960:Hyaluronan Receptors; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D020382:Interleukin-18; D000067596:Interleukin-33; D007378:Interleukins; D016328:NF-kappa B; D009844:Oligosaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D006820:Hyaluronic Acid