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Inhibition of the hyaluronan oligosaccharides inflammatory response: reduction of adenosine 2A receptor activation by EPAC and PKA
Author(s) -
Campo Giuseppe M.,
Avenoso Angela,
D'Ascola Angela,
Scuruchi Michele,
Nastasi Giancarlo,
Calatroni Alberto,
Campo Salvatore
Publication year - 2014
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3073
Subject(s) - chemistry , adenosine , cyclic adenosine monophosphate , receptor , messenger rna , signal transduction , tumor necrosis factor alpha , microbiology and biotechnology , biochemistry , endocrinology , biology , gene
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 © 2014 John Wiley & Sons, Ltd.