期刊
CELL BIOCHEMISTRY AND FUNCTION
卷 32, 期 8, 页码 692-701出版社
WILEY
DOI: 10.1002/cbf.3073
关键词
inflammation; adenosine; hyaluronan; synoviocytes; TLRs; cytokines; EPAC
资金
- grant COFIN of Ministero dell'Istruzione, dell'Universita e della Ricerca, Italy [20094C2H2M_003]
The aim of this study was to investigate the involvement of exchange proteins directly activated by cyclic adenosine (ADO) monophosphate (EPAC) in 4-mer hyaluronan (HA) oligosaccharide-induced inflammatory response in mouse normal synovial fibroblasts (NSF). Treatment of NSF with 4-mer HA increased Toll-like receptor-4, TNF-alpha and IL-1beta mRNA expression and of the related proteins, as well as nuclear factor kappaB (NF-kB) activation. Addition to NSF, previously stimulated with 4-mer HA oligosaccharides, of ADO significantly reduced NF-kB activation, TNF-alpha and IL-1beta expression. The pre-treatment of NSF with cyclic ADO monophosphate and/or PKA and/or EPAC-specific inhibitors significantly inhibited the anti-inflammatory effect exerted by ADO. In particular, the EPAC inhibitor reduced the ADO effect to a major extent than the PKA inhibitor. These results mean that both PKA and EPAC pathways are involved in ADO-induced NF-kB inhibition although EPAC seems to be more involved than PKA. Copyright (c) 2014 John Wiley & Sons, Ltd.
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