A 2A R regulate inflammation through PKA/NF-κB signaling pathways in intervertebral disc degeneration.

Background: Reduction of inflammatory damage and inhibition of nucleus pulposus (NP) apoptosis are considered to be the main effective therapy idea to reverse the intervertebral disc degeneration (IDD) and alleviate the chronic low back pain. The adenosine A2A receptor (A2AR), as a member of G protein-coupled receptor families, plays an important role in the anti-inflammation and relieving pain. So far, the impact of A2AR on IDD therapy is unclear. The aim of this study was to explore the role of Adenosine A _2A receptor (A _2A R) in the intervertebral disc degeneration (IDD) and clarify potential mechanism.
Materials and Methods: IL-1β and acupuncture was used to establish IDD model rats. A _2A R agonist CGS-21680 and A _2A R antagonist SCH442416 were used to investigate the therapeutical effects for IDD. Histological examination, western blotting analysis and RT-PCR were employed to evaluate the the association between A _2A R and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway.
Results: A _2A R activity of the intervertebral disc tissues was up-regulated in feedback way, and cAMP, PKA and CREB expression were also increased. But in general, IL-1β-induced IDD promoted the significant up-regulation the expression of inflammatory factors. The nucleus pulposus (NP) inflammation was exacerbated in result of MMP3 and Col-II decline through activating NF-κB signaling pathway. A _2A R agonist CGS-21680 exhibited a disc protective effect through significantly increasing A _2A R activity, then further activated cAMP/PKA signaling pathway with attenuating the release of TNF-α and IL-6 via down-regulating NF-κB. In contrast, SCH442416 inhibited A _2A R activation, consistent with lower expression levels of cAMP and PKA, further leading to the acceleration of IDD.
Conclusions: The activation of A _2A R can prevent inflammatory responses and mitigates degradation of IDD thus suggest a potential novel therapeutic strategy of IDD.
(© 2024. The Author(s).)