Cannabidiol alters the immune response to Porphyromonas gingivalis in mice.

alveolar bone loss;cannabidiol;CB2;periodontitis;phtocannadbinoids;porphyromanas gingivalis

Shilpa Singh

University:University of Louisville

Department:Oral Biology

关键词: alveolar bone loss;    cannabidiol;    CB2;    periodontitis;    phtocannadbinoids;    porphyromanas gingivalis;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=4228&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Background: Porphyromonas gingivalis is an important etiologic agent of chronic periodontitis, an infectious disease defined by destruction of supporting tissues of the teeth. Marijuana is a risk factor for chronic periodontitis, although underlying mechanisms are poorly understood. As phytocannabinoids have been ascribed antiinflammatory properties, we hypothesized that cannabidiol exposure would lead to altered immune response to P. gingivalis infection facilitating bacterial persistence and, subsequently, increased alveolar bone loss in cannabidiol (CBD)-exposed mice. Methods: P. gingivalis-infected cannabinoid receptor 2 (CB2) knockout and wild type C57/Bl6 mice were exposed, or not exposed, to cannabidiol. Oral swabs from mice were used to monitor the presence of P. gingivalis by PCR and culture. Skulls were harvested, defleshed and stained to analyze the amount of bone loss under microscope. Alveolar bone volume and alveolar bone density were also analyzed by using CT. Systemic P. gingivalis-specific and total IgG and IgM antibodies were quantified by ELISA. Periodontal expression of inflammatory markers – CD14, CD45, MIP-2, MMP-9 and IL-1β was measured in the maxillary gingivae by qPCR. Results: In our hands oral gavage model appears to be one of repeated transient infection with P. gingivalis rather than a persistent colonization model. Although P. gingivalis could not be detected in oral swabs, the infection was sufficient to produce an immune reaction in gingiva and serum. Cannabidiol suppresses total IgM production in mice. If this occurs in humans, it applies that adaptive immune response is less well equipped for the arrival of oral pathogens. However, CBD did not affect P. gingivalis specific IgG response. CBD significantly reduced the expression of IL-1β, CD45 and CD14 inflammatory markers in maxillary gingiva in P. gingivalis infected wild type mice but not CB2 -/- mice. Deficient immune response to P. gingivalis may lead to its persistence and more severe periodontal destruction in cannabis users. This is analogous with in-vitro nicotine studies and with clinical studies showing more severe clinical manifestations of chronic periodontitis in tobacco smokers. However, our results showed a reduction in MMP-9 expression in presence of cannabidiol. This anomaly is hard to explain and does not correspond with the findings in cigarette smokers where MMP-9 levels are significantly higher. Increased bone loss was hypothesized because we know cannabis drives bone loss in animals and humans. This did not happen here. May be because we didn’t have persistent infection. However, immune differences between wild type versus knock out mice suggest that we