The adenosine 2A receptor (A2AR) is greatly involved in inflammation pathologies such as rheumatoid arthritis. 24 By interacting with A2AR, the purine nucleoside adenosine acts as a potent endogenous inhibitor of the inflam- 25 matory process in a variety of tissues. Hyaluronan (HA) fragments act to prime inflammation via CD44 and the 26 toll-like receptor 4 (TLR-4). The aim of this study was to investigate whether the inhibition/stimulation of 27 A2AR modulates the inflammation cascade primed by small HA fragments in mouse articular chondrocytes. 28 6-mer HA treatment induced up-regulation of CD44, TLR4 and A2AR mRNA expression and the related protein 29 levels, and NF-kB activation, that in turn increased TNF-α, IL-1β, and IL-6 and production. Treatment with a 30 selective 2A adenosine receptor agonist (2-phenylaminoadenosine) enhanced A2AR increase, as well as the 31 inhibition of CD44 and TLR4 activity using two specific antibodies, abolished up-regulation of CD44 and 32 TLR4, and significantly reduced, especially by antibody inhibition, NF-kB activation and pro-inflammatory 33 cytokine production. Furthermore, the exposure of chondrocytes to A2AR specific interference mRNA (A2AR 34 siRNA) enhanced HA 6-mer induced NF-kB activation and inflammatory cytokine increase. Finally, the use 35 of an exchange protein activated by cAMP (EPAC) siRNA and a specific PKA inhibitor showed a predominant 36 EPAC involvement in the mediation of the anti-inflammatory activity exerted by A2AR stimulation. 37 These data suggest that HA depolymerization occurring during inflammation contributes to priming of the 38 inflammatory cascade, while endogenous adenosine, by exerting anti-inflammatory response via A2AR, 39 could be a modulatory mechanism that attempts to attenuate the inflammation process.

The stimulation of adenosine 2A receptor reduces inflammatory response in mouse articular chondrocytes treated with hyaluronan oligosaccharides

CAMPO, Giuseppe Maurizio;AVENOSO, Angela;D'ASCOLA, ANGELA;Scuruchi M;CALATRONI, Alberto;CAMPO, Salvatore Giuseppe
2012-01-01

Abstract

The adenosine 2A receptor (A2AR) is greatly involved in inflammation pathologies such as rheumatoid arthritis. 24 By interacting with A2AR, the purine nucleoside adenosine acts as a potent endogenous inhibitor of the inflam- 25 matory process in a variety of tissues. Hyaluronan (HA) fragments act to prime inflammation via CD44 and the 26 toll-like receptor 4 (TLR-4). The aim of this study was to investigate whether the inhibition/stimulation of 27 A2AR modulates the inflammation cascade primed by small HA fragments in mouse articular chondrocytes. 28 6-mer HA treatment induced up-regulation of CD44, TLR4 and A2AR mRNA expression and the related protein 29 levels, and NF-kB activation, that in turn increased TNF-α, IL-1β, and IL-6 and production. Treatment with a 30 selective 2A adenosine receptor agonist (2-phenylaminoadenosine) enhanced A2AR increase, as well as the 31 inhibition of CD44 and TLR4 activity using two specific antibodies, abolished up-regulation of CD44 and 32 TLR4, and significantly reduced, especially by antibody inhibition, NF-kB activation and pro-inflammatory 33 cytokine production. Furthermore, the exposure of chondrocytes to A2AR specific interference mRNA (A2AR 34 siRNA) enhanced HA 6-mer induced NF-kB activation and inflammatory cytokine increase. Finally, the use 35 of an exchange protein activated by cAMP (EPAC) siRNA and a specific PKA inhibitor showed a predominant 36 EPAC involvement in the mediation of the anti-inflammatory activity exerted by A2AR stimulation. 37 These data suggest that HA depolymerization occurring during inflammation contributes to priming of the 38 inflammatory cascade, while endogenous adenosine, by exerting anti-inflammatory response via A2AR, 39 could be a modulatory mechanism that attempts to attenuate the inflammation process.
2012
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/2327856
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 24
social impact