David A. Scott, PhD

David A. Scott, PhD

David A. Scott, PhD

ProfessorDavid A. Scott, PhD
Department of Oral Immunology and Infectious Diseases 
Phone: 502-852-8905
Email: david.scott@louisville.edu

Tobacco, marijuana, inflammation and periodontal diseases

Chronic periodontitis is a common inflammatory disease defined by the irreversible destruction of the supporting tissues of the teeth. Tobacco and cannabis smoking are critical risk factors for this and other chronic inflammatory diseases. The mechanisms by which smoking contributes to increased susceptibility to periodontitis, and to systemic inflammatory diseases with common etiology, need to be clarified. Thus, novel therapeutic strategies can be identified to treat tobacco-induced diseases, the world’s largest cause of early fatality. We are particularly interested in (a) how tobacco-induced genotypic and phenotypic alterations to oral bacterial pathogens change how such microbes are recognized by the immune system; (b) how tobacco- and marijuana-derived molecules erroneously activate endogenous anti-inflammatory pathways, such as nicotinic cholinergic signaling, and thus suppresses the ability of the immune system to fight off periodontal pathogens; and (c) better understanding the cross-talk between exogenous (e.g., nicotine, phytocannabinoids) and endogenous (e.g. resolvins, acetylcholine) anti-inflammatory agents, with a focus on the central innate mediator, GSK3β.

GSK3β inhibition abrogates pathogen-induced bone loss. 8-12 week old B6129SF2/J mice were randomly divided into three control groups and two experimental groups (n = 5 per group). The control groups were treated with cellulose (sham infected), 0.02% DMSO, or SB216763 (10 mg/kg) respectively. The experimental groups were orally infected with P. gingivalis 33277 with or without pretreatment of the GSK3 inhibitor, SB216763 (10 mg/kg). Alveolar bone loss was visualized by methylene blue / eosin staining six weeks later.  Typical maxillae from (A) sham-infected, (B) P. gingivalis-infected, and (C) SB216763-treated, P. gingivalis-infected mice are presented. (D) The distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) was measured 6 weeks post infection at 14 predetermined maxillary buccal sites, marked by yellow diamonds,  in 8-12 week old B6129SF2/J mice divided into three control (cellulose; DMSO; or SB216763 treated) and two experimental (P. gingivalis-infected; and SB216763-treated, P. gingivalis-infected mice) groups. Data are presented as mean distance CEJ-ABC in mm ± s.d. where there are 5 mice per group. Symbols: * p < 0.05 compared to P. gingivalis treated group; ** p < 0.01 compared to P. gingivalis treated group. (Molecular Medicine 2012, 18: 1190-6).  

 

Current Funding:

- Tobacco -induced alterations to P. gingivalis-host interactions; NIH/NIDCR R01 DE019826.

- P. gingivalis: Role of GSK3 in host inflammation; NIH/NIDCR R01 DE017680.

Recent publications

  1. Simsik N, Zeller I, Renaud DE, Buduneli N, Severcan F, Scott DA*. Differentiation of chronic and aggressive forms of periodontitis by Fourier-transform infrared spectroscopy. Journal of Dental Research 2016;95:1472-1478.
  2. Goulas T, Ferrer I, Hutcherson JA, Potempa B, Potempa J, Scott DA*, Gomis-Ruth FX. Structure of RagB, a major immunodominant outer-membrane surface receptor antigen of Porphyromonas gingivalis. Molecular Oral Microbiology2016:31;472-485.
  3. Hutcherson JA, Gogeneni H, Yoder-Himes D, Hendrikson E, Hackett M, Whiteley M, Lamont RJ, Scott DA*.Comparison of inherently essential genes of Porphyromonas gingivalis identified in two transposon sequencing libraries. Molecular Oral Microbiology2016;31:354-364.
  4. Gao S, Li S, Ma Z, Liang S, Shan T, Zhang M, Zhu X, Zhang P, Liu G, Zhou F, Yuan X, Jia R, Tai E, Potempa J, Scott DA*, Lamont RJ, Wang H,  Feng X. Negative correlation between Porphyromonas gingivalis and clinicopathological characteristics and survival in patients with esophageal squamous cell carcinoma. Infectious Agents and Cancer 2016;11:3.
  5. Yin H, Zhou H, Kang Y, Zhang X, Duan X, Liang S, Scott DA*, Lamont RJ, Shang J, Wang H. Syk negatively regulates TLR4-mediated IFN&#945; and IL-10 production and promotes inflammatory responses in dendritic cells. BBA General Subjects 2016;1860:588-598.
  6. Gu Z, Lamont GJ, Lamont RJ, Uriarte S, Wang H, Scott DA*. Resolvin D1, resolvin D2 and maresin 1 activate the GSK3&#946; anti-inflammatory axis in TLR4-engaged human monocytes. Innate Immunity 2016;22:186-195
  7. Wang H, Graves II M, Zhou H, Gu Z, Lamont RJ, Scott DA*. 2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine is an anti-inflammatory TLR-2, -4 and -5 response mediator in human monocytes. Inflammation Research2016;65:61-69. Wang Q, Sztukowska M, Ojo A, Scott DA*, Wang H, Lamont RJ. FOXO responses to Porphyromonas gingivalis in epithelial cells. Cellular Microbiology 2015;17:1605-17.
  8. Zhou Y, Sztukowska M , Wang Q, Inaba H, Potempa J, Scott DA*, Wang H, Lamont RJ. Noncanonical activation of β-catenin by Porphyromonas gingivalis. Infection and Immunity 2015;83:3195-203.
  9. Zhou H, Gao S, Duan X, Liang L, Scott DA*, Lamont RJ, Wang H. Inhibition of serum- and glucocorticoid- inducible kinase1 enhances TLR-mediated inflammation and promotes endotoxin-driven organ failure. FASEB Journal 2015;29:3737-49.
  10. Hutcherson JA, Bagaitkar J, Nagano K, Yoshimura F, Wang H, Scott DA*. Porphyromonas gingivalis RagB is a pro-inflammatory STAT4 agonist.Molecular Oral Microbiology 2015;30:242-52.
  11. Gogeneni H, Buduneli N, Ceyhan-Ozturk B, Gumus G, Akcali A, Renaud DE, Scott DA*, Ozcaka O. Increased infection with key periodontal pathogens during gestational diabetes mellitus. Journal of Clinical Periodontology 2015;42:506-12. Hutcherson JA, Bagaitkar J, Scott DA*. Scratching the surface - tobacco-induced bacterial biofilms.Tobacco Induced Diseases (invited review). 2015;13:e1.
  12. Wang H, Zhou H, Duan X, Jotwani R, Vuddaraju H, Liang S, Scott DA*, Lamont RJ. Porphyromonas gingivalis-induced reactive oxygen species activate JAK2 and regulate the production of inflammatory cytokines through C-JUN. Infection and Immunity 2014;82:4118-26.
  13. Scott DA*, Lamont RJ, Wang H. GSK3&#946; and the control of infectious bacterial diseases. Trends in Microbiology 2014;22:208-17.PMC4003878. IF = 8.9.
  14. Zeller I, Hutcherson JA, Lamont RJ, Demuth DR, Gumus P, Nizam N, Buduneli N, Scott DA*. Altered antigenic profiling and infectivity of Porphyromonas gingivalis in smokers and non-smokers with periodontitis. Journal of Periodontology (in press, 2014).
  15. Kaval B, Renaud DE, Scott DA*, Buduneli N. The role of smoking and gingival crevicular fluid markers on coronally advanced flap outcomes. Journal of Periodontology (in press, 2014).
  16. Wang H, Brown J, Gao S, Liang S, Jotwani R, Zhou H, Suttles J, Scott DA*, Lamont RJ. The role of JAK-3 in regulating TLR-mediated inflammatory cytokine production in innate immune cells. Journal of Immunology 2013;191:1164-74.
  17. Bondy-Carey JL, Galicia J, Bagaitkar J, Potempa JS, Potempa B, Kinane DF, Veillard F, Scott DA*. Neutrophils alter epithelial response to Porphyromonas gingivalis in a gingival crevice model. Molecular Oral Microbiology 2013:102-13.
  18. Adamowicz K, Wang H, Jotwani R, Zeller I, Potempa J, Scott DA*. Inhibition of GSK3 abolishes bacterial-induced periodontal bone loss in mice. Molecular Medicine 2012, 18: 1190-6.
  19. Scott DA andJ Krauss. Neutrophils in periodontal inflammation. Frontiers in Oral Biology 2012;15:56-83.
  20. Bagaitkar J, Daep CA, Patel CK, Renaud DE, Demuth DR, Scott DA*. Tobacco smoke augments Porphyromonas gingivalis-Streptococcus gordonii biofilm formation. PLoS One 2011;6:e27386.
  21. Bagaitkar J, Zeller I, Renaud DE, Scott DA*. Cotinine inhibits the pro-inflammatory response initiated by multiple cell surface Toll-like receptors in monocytic THP cells. Tobacco Induced Diseases 2012;10:18.
  22. Guzik K, Skret J, Smagur J, Bzowska M, Gajkowska B, Scott DA*, Potempa JS. Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages. Cell Death and Disease 2011;2:e131.
  23. Buduneli N, Larsson L, Biyikoglu B, Renaud DE, Bagaitkar J, ScottDA*. Fatty acid profiles in smokers with chronic periodontitis. Journal of Dental Research 2011;90:47-52
  24. Bagaitkar J, Demuth DR, Daep CA, Renaud DE, Pierce DL, Scott DA*. Tobacco upregulates P. gingivalis fimbrial proteins which induce TLR2 hyposensitivity. PLoS One 2010;5:e9323.
  25. Xiang XM, Liu KZ, Man A, Ghiabi E, Cholakis A, Scott DA*. Periodontitis-specific molecular signatures in gingival crevicular fluid. Journal of Periodontal Research 2010;45:345-52.
  26. Bagaitkar J, Williams LR, Renaud DE, Bemakanakere MR, Martin M, Demuth DR, Scott DA*. Tobacco-induced alterations to Porphyromonas gingivalis-host interactions. Environmental Microbiology 2009;11:1242-53.


MAJOR COLLABORATORS

Drs. Bagaitkar, Richard Lamont, Jan Potempa and Huizhi Wang (Oral Immunology and Infectious Diseases, UofL).

Dr. Sylvia Uriarte (Nephrology, UofL)

Dr. Debbie Yoder-Himes (Biology, UofL)

Dr. Nurcan Buduneli (Periodontics, Ege University, Turkey).

Dr. Jackie Singleton (Dental Hygiene, UofL).


Graduate students

Graduate students who wish to pursue a M.Sc. in Oral Biology or Ph.D. (Microbiology & Immunology; Pharmacology & Toxicology; or Interdisciplinary Studies) are periodically accepted. Interested individuals should e-mail me directly.

Clinical graduate students already at University of Louisville who wish to consider undertaking the research component of their program in my laboratory should e-mail or call into the lab (School of Dentistry, Room 260) in person.