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Danger signal adenosine via adenosine 2a receptor stimulates growth of P orphyromonas gingivalis in primary gingival epithelial cells
Author(s) -
Spooner R.,
DeGuzman J.,
Lee K.L.,
Yilmaz Ö.
Publication year - 2014
Publication title -
molecular oral microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 77
eISSN - 2041-1014
pISSN - 2041-1006
DOI - 10.1111/omi.12045
Subject(s) - adenosine , adenosine receptor , receptor , purinergic signalling , adenosine a2b receptor , adenosine a3 receptor , microbiology and biotechnology , agonist , cgs 21680 , signal transduction , adenosine a2a receptor , biology , porphyromonas gingivalis , chemistry , pharmacology , endocrinology , medicine , biochemistry , periodontitis
Summary Extracellular signaling during inflammation and chronic diseases involves molecules referred to as ‘ D anger S ignals’ ( DS ), including the small molecule adenosine. We demonstrate that primary gingival epithelial cells ( GEC ) express a family of G ‐protein coupled receptors known as adenosine receptors, including the high‐affinity receptors A 1 and A 2a and low‐affinity receptors A 2b and A 3. Treatment of Porphyromonas gingivalis ‐infected GEC with the A 2a receptor‐specific agonist CGS ‐21680 resulted in elevated intracellular bacterial replication as determined by fluorescence microscopy and antibiotic protection assay. Additionally, A 2a receptor antagonism and knockdown via RNA interference significantly reduced metabolically active intracellular P. gingivalis . Furthermore, analysis of anti‐inflammatory mediator cyclic AMP (c AMP ) following A 2a receptor selective agonist CGS ‐21680 stimulation induced significantly higher levels of c AMP during P. gingivalis infection, indicating that adenosine signaling may attenuate inflammatory processes associated with bacterial infection. This study reveals that the GEC express functional A 2a receptor and P. gingivalis may use the A 2a receptor coupled DS adenosine signaling as a means to establish successful persistence in the oral mucosa, possibly via downregulation of the pro‐inflammatory response.