194 NPY Y1, IL-1RI, and Adrenergic Receptors Modulate P. gingivalis-Induced Inflammation

Thursday, March 22, 2012: 10:45 a.m. - 12:15 p.m.
Presentation Type: Oral Session
B.F. READER1, C. IGBOIN2, G. LEYS3, M. BAILEY4, B. LEBLEBICIOGLU5, N.D. POWELL3, and J.F. SHERIDAN3, 1Oral Biology, Institute for Behavioral Medicine Research, Ohio State University, Columbus, OH, 2OHIO STATE UNIVERSITY, Columbus, OH, 3College of Dentistry, Ohio State University, Columbus, OH, 4College of Dentistry, The Ohio State University, Columbus, OH, 5Ohio State University, Columbus, OH
Periodontitis is a common polymicrobial inflammatory disease that can progress to severe tissue destruction and tooth loss. Porphyromonas gingivalis (P. gingivalis) is associated with periodontitis, and has been successfully used in experimental models to replicate the inflammation seen in clinical cases. Neuropeptide Y (NPY) and its Y1 receptor (Y1R) are present in the periodontium and may play a role in this inflammation by modulating norepinephrine, which, via β-adrenergic receptors (β-ARs), may modulate proinflammatory cytokines. Induction of cytokines, such as Interleukin-1β (IL-1β), can promote periodontitis-associated inflammation and precipitate the subsequent deleterious effects.

Objective: To determine whether manipulating the actions of NPY, norepinephrine, or IL-1β modulates proinflammatory cytokine gene expression during P. gingivalis-induced inflammation.


Methods: IL-1 Receptor Type I (IL-1RI) knockout mice or wild-type mice administered Y1R antagonist or α- and β -AR agonists and antagonists were injected with live P. gingivalis or vehicle into tissues over the calvaria. After 1 or 3 days, the tissues were processed for quantitative PCR and gene expression was determined for IL-1β, IL-6, and TNF-α. 

Results:  Gene expression of proinflammatory cytokines was potentiated with the blockade of Y1Rs or both central and peripheral β2-ARs, while antagonizing peripheral β-ARs alone decreased expression. Agonizing α1- or β2-ARs, or antagonizing β1-ARs resulted in decreased expression. Non-specifically antagonizing α-ARs also resulted in decreased expression pointing to a role for α2-ARs in this inflammation model. 

Conclusion: Taken together these data suggest that during P. gingivalis-induced inflammation IL-1RI receptors are necessary for proinflammatory cytokine expression (IL-6 and TNF-α) and that the Y1Rs and ARs regulate proinflammatory gene expression with the central β2-adrenergic receptors playing a critical role in this regulation. Since NPY, IL-1β, and norepinephrine have been implicated in the stress response, exploring these mechanisms will not only aid in identifying novel therapeutic targets, but elucidate the connection of stress to periodontitis.

This abstract is based on research that was funded entirely or partially by an outside source: NIDCR 1F31DE021638-01A1

Keywords: Bacterial, Gene expression, Immunology, Periodontal disease and Stress