title: Downregulation of Proteinase-Activated Receptor-2, Interleukin-17, and Other Proinflammatory Genes by Subantimicrobial Doxycycline Dose in a Rat Periodontitis Model.
abstract: BACKGROUND
  Subantimicrobial dose doxycycline (SDD) has been used as an adjunct in periodontal treatment because of its matrix metalloproteinase inhibition properties. Although the benefits of SDD therapy, such as improvement in the parameters of periodontal probing depth and clinical attachment level, have been proven in multiple clinical studies, the comprehension of other biologic mechanisms of action on periodontitis remains poorly investigated. Therefore, this animal-model study evaluated the effects of SDD monotherapy on the expressions of the following key proinflammatory genes: proteinase-activated receptor-2 (PAR2), tumor necrosis factor (TNF)-α, interleukin (IL)-17, and IL-1β.
  
  
  METHODS
  Male Wistar rats were assigned randomly to the following: 1) control group: no ligature-induced periodontitis and no treatment; 2) ligature group: ligature-induced periodontitis and placebo treatment; and 3) ligature + doxycycline group: ligature-induced periodontitis and SDD treatment. After the experimental time, animals were sacrificed, and reverse transcription-polymerase chain reaction was performed to analyze the mRNA expression of IL-1β, IL-17, TNF-α, and PAR2 in gingival tissue samples. Histologic analyses were performed on the furcation region and mesial gingiva of mandibular first molars to measure periodontal bone loss and collagen content.
  
  
  RESULTS
  SDD administration significantly downregulated PAR2, IL-17, TNF-α, and IL-1β mRNA expressions (P <0.05). In addition, SDD treatment was accompanied by lower rates of alveolar bone loss (P <0.05) and maintenance of the amount of gingival collagen fibers.
  
  
  CONCLUSIONS
  These findings reveal new perspectives regarding SDD efficacy because it can be partially related to proinflammatory gene expression modulation, even considering PAR2 and IL-17, which has not been investigated thus far.
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, São Paulo, Brazil.
authors.forename: Myrella L
authors.initials: ML
authors.lastname: Castro
authors.affiliation: Department of General Biology, State University of Ponta Grossa, Ponta Grossa, Paraná, Brazil.
authors.forename: Gilson C N
authors.initials: GC
authors.lastname: Franco
authors.affiliation: Department of Dentistry II, Federal University of Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Branco-de-Almeida
authors.affiliation: Department of Bioscience and Oral Diagnosis, Institute of Science and Technology-São José dos Campos, Paulista State University, São Paulo, São Paulo, Brazil.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Anbinder
authors.affiliation: Department of Dentistry, Implantology Area, University of Santo Amaro, São Paulo, São Paulo, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Cogo-Müller
authors.affiliation: Nucleus of Periodontal Research, University of Taubaté, Taubaté, São Paulo, Brazil.
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Cortelli
authors.affiliation: Department of Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, NY.
authors.forename: Simone
authors.initials: S
authors.lastname: Duarte
authors.affiliation: Department of Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, NY.
authors.forename: Deepak
authors.initials: D
authors.lastname: Saxena
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, São Paulo, Brazil.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Rosalen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D015536:Down-Regulation; D004318:Doxycycline; D020381:Interleukin-17; D008297:Male; D010518:Periodontitis; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2
chemical_list: D000900:Anti-Bacterial Agents; C515934:Il17a protein, rat; D020381:Interleukin-17; D044464:Receptor, PAR-2; D004318:Doxycycline
keywords: Alveolar bone loss; doxycycline; periodontal diseases; receptor, PAR-2