4-Mer Hyaluronan Oligosaccharides Stimulate Inflammation Response in Synovial Fibroblasts in Part via Tak-1 and in Part via P38-Mapk
| Autor: | Angela Avenoso, Vera Prestipino, Alberto Calatroni, Michele Scuruchi, Salvatore Campo, Giancarlo Nastasi, Giuseppe M. Campo, Angela D'Ascola |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
MAPK/ERK pathway medicine.medical_specialty p38 mitogen-activated protein kinases Interleukin-1beta Nitric Oxide Synthase Type II Arthritis Inflammation p38 Mitogen-Activated Protein Kinases Biochemistry Proinflammatory cytokine Mice Downregulation and upregulation Internal medicine Matrix Metalloproteinase 13 Drug Discovery medicine Animals RNA Messenger Hyaluronic Acid Protein kinase A Cells Cultured Pharmacology Chemistry Synovial Membrane Organic Chemistry NF-kappa B Fibroblasts MAP Kinase Kinase Kinases medicine.disease Arthritis Experimental Molecular biology Toll-Like Receptor 2 Up-Regulation Toll-Like Receptor 4 Hyaluronan Receptors Endocrinology MAPK TAK-1 hyaluronan inflammation Mice Inbred DBA Molecular Medicine medicine.symptom Transforming growth factor |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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