Date on Master's Thesis/Doctoral Dissertation
Oral Biology, MS
Committee Co-Chair (if applicable)
cannabinoids; inaate immunity; P. gingivalis; chronic periodontitis
Marijuana is widely used in the United States for recreational and medicinal purposes. Despite the proposed beneficial effects of cannabis on certain medical conditions, there is also a concern there is also a concern over negative health consequences of marijuana smoking. Recently, cannabis use has been established as a dose related risk factor for chronic periodontitis. Although the induction / exacerbation of chronic periodontitis in marijuana users has been established epidemiologically, the mechanisms underlying such predisposition are still unknown. It has long been suggested that marijuana has anti-inflammatory properties, while human epithelial cells are known to express cannabinoid receptor type 2 (CB2). Therefore, we hypothesized that marijuana-derived cannabinoids may suppress the innate immune response, altering the ability of gingival epithelial cells to respond appropriately to bacterial stimuli (the classic TLR4 ligand, E. coli LPS; and the major periodontal vii pathogen, Porphyromonas gingivalis). More specifically, we hypothesized that predominant phytocannabinoid subtypes (cannabidiol [CBD], cannabinol [CBN], or tetrahydrocannabinol [THC]) at physiologically relevant doses (0 - 10µg/ml) would suppress proinflammatory cytokine production in LPS- (0-1µg/ml) or P. gingivalis (MOI, 10:1) exposed telomerase immortalized human gingival keratinocytes (TIGK cells) in a CB2-related manner. We also hypothesized that marijuana-derived cannabinoids may influence the viability of both epithelial (TIGK cells, as assessed by Trypan blue exclusion) and representative oral bacteria (P. gingivalis, Treponema denticola and Filifactor alocis, growth curves monitored by optical density). Higher doses (>5 µg/ml) of marijuana derived cannabinoids (CBD, CBN or THC) inhibited the growth of P. gingivalis (p < 0.001) and F. alocis (p < 0.001), relative to unexposed bacteria, whereas T. denticola growth was resistant to all cannabinoid doses tested (1- 10 µg/ml, p > 0.05).. TIGK cells were non-viable when exposed to high cannabinoid concentrations (> 10 µg/ml).Sub-lethal (1 -5 µg/ml) doses of each cannabinoid subtype suppressed the production of IL-8 and IL-6 but enhanced IL-10 release in P. gingivalis or LPS stimulated TIGKs (all p < 0.001). Treatment with the CB2 inhibitor, JTE907, did not rescue cannabinoid-induced immune suppression, suggesting that alternative cannabinoid receptors, such as CB1, GPR55 or A2A receptors, may be associated with the anti YLLL inflammatory function of marijuana-derived cannabinoids. If the phenomena of (i) cannabinoid induced epithelial toxicity; (ii) growth restriction of a sub-population of bacterial species in the oral biofilm; and (iii) innate suppression in gingival epithelial cells, established herein, occur in vivo, they are likely to help explain increased susceptibility to periodontal diseases in cannabis users. To expand, the epithelial barrier may be compromised in marijuana smokers, facilitating bacterial entry and more efficient diffusion of microbial toxins into the gingival tissues; marijuana-derived cannabinoids may promote microbial dysbiosis; and a suppressed pro-inflammatory epithelial response to bacterial stimuli may promote immune evasion, colonization and persistence by pathogenic bacteria. These data provide some of the first mechanistic insights into cannabinoid associated periodontal diseases. Such mechanistic advance are critical if novel therapeutics to prevent chronic periodontitis in marijuana users are to be developed. Further, an improved understanding of the immuneregulatory properties of cannabinoids will be useful in the development of therapeutics for the containment of inflammation, in general.
Guha Niyogi, Rajarshi, "Cannabinoids suppress the innate immune response to periodontal pathogen Porphyromonas gingivalis in gingival epithelial cells." (2016). Electronic Theses and Dissertations. Paper 2503.