Provider: Ingenta Connect Database: Ingenta Connect Content: application/x-research-info-systems TY - ABST AU - M. Campo, G. AU - Avenoso, A. AU - D’Ascola, A. AU - Prestipino, V. AU - Scuruchi, M. AU - Nastasi, G. AU - Calatroni, A. AU - Campo, S. TI - 4-Mer Hyaluronan Oligosaccharides Stimulate Inflammation Response in Synovial Fibroblasts in Part via TAK-1 and in Part via p38-MAPK JO - Current Medicinal Chemistry PY - 2013-03-01T00:00:00/// VL - 20 IS - 9 SP - 1162 EP - 1172 KW - toll-like receptors KW - cytokines KW - TAK-1 KW - Hyaluronan KW - NF-kB KW - p38-MAPK KW - RASF KW - pro-inflammatory effects KW - oligosaccharides KW - 4-mer hyaluronan (HA) N2 - 4-mer hyaluronan (HA) oligosaccharides stimulate pro-inflammatory effects in different cell types by interacting with both the toll-like receptor-4 (TLR-4) and -2 (TLR-2). This interaction induces the activation of the transforming growth factor activated kinase-1 (TAK-1) that activates the nuclear factor kappaB (NF-kB) either directly and/or through the activation of p38-mitogen-activated protein kinase (p38-MAPK). This in turn induces the transcription of proinflammatory mediators that prime inflammation. Our aim was to investigate the involvement of TAK-1 and p38-MAPK in 4-mer HA oligosaccharide-induced inflammatory response in mouse synovial fibroblasts obtained from normal DBA/J1 mice (NSF) and from mice subjected to collagen-induced arthritis (CIA). Treatment of NSF and rheumatoid arthritis synovial fibroblasts (RASF) with 4-mer HA showed a marked up-regulation of TLR-4, TLR-2, TAK-1 and p38-MAPK mRNA expression and of the related proteins, as well as NF-kB activation. High levels were also detected of TNF-α, IL- 1β, MMP-13 and iNOS. Treatment of NSF and RASF, previously stimulated with 4-mer HA oligosaccharides, with TAK- 1 and/or p38-MAPK specific inhibitors significantly reduced all the parameters, although the inhibitory effect of p38- MAPK was less effective than that of TAK-1. The addition of CD44 antibody to both NSF and RASF showed that CD44 was not involved in 4-mer HA-induced inflammation. UR - https://www.ingentaconnect.com/content/ben/cmc/2013/00000020/00000009/art00005 ER -