Downregulation of proteinase-activated receptor-2, interleukin-17, and other proinflammatory genes by subantimicrobial doxycycline dose in a rat periodontitis model

Myrella L. Castro, Gilson C.N. Franco, Luciana S. Branco-De-almeida, Ana L. Anbinder, Karina Cogo-Müller, Sheila C. Cortelli, Simone Duarte, Deepak Saxena, Pedro L. Rosalen

Research output: Contribution to journalArticle

12 Citations (Scopus)

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: proteinaseactivated receptor-2 (PAR2), tumor necrosis factor (TNF)-a, interleukin (IL)-17, and IL-1b. Methods: Male Wistar rats were assigned randomly to the following: 1) control group: no ligatureinduced 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-1b, IL-17, TNF-a, 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-a, and IL-1b 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalJournal of Periodontology
Volume87
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Fingerprint

PAR-2 Receptor
Interleukin-17
Doxycycline
Periodontitis
Down-Regulation
Genes
Ligation
Interleukins
Interleukin-17 Receptors
Alveolar Bone Loss
Collagen
Therapeutics
Tumor Necrosis Factor-alpha
Receptors, Tumor Necrosis Factor, Type II
Messenger RNA
Gingiva
Matrix Metalloproteinases
Reverse Transcription
Wistar Rats
Animal Models

Keywords

  • Alveolar bone loss
  • Doxycycline
  • PAR-2
  • Periodontal diseases
  • Receptor

ASJC Scopus subject areas

  • Periodontics

Cite this

Castro, M. L., Franco, G. C. N., Branco-De-almeida, L. S., Anbinder, A. L., Cogo-Müller, K., Cortelli, S. C., ... Rosalen, P. L. (2016). Downregulation of proteinase-activated receptor-2, interleukin-17, and other proinflammatory genes by subantimicrobial doxycycline dose in a rat periodontitis model. Journal of Periodontology, 87(2), 203-210. https://doi.org/10.1902/jop.2015.150385

Downregulation of proteinase-activated receptor-2, interleukin-17, and other proinflammatory genes by subantimicrobial doxycycline dose in a rat periodontitis model. / Castro, Myrella L.; Franco, Gilson C.N.; Branco-De-almeida, Luciana S.; Anbinder, Ana L.; Cogo-Müller, Karina; Cortelli, Sheila C.; Duarte, Simone; Saxena, Deepak; Rosalen, Pedro L.

In: Journal of Periodontology, Vol. 87, No. 2, 01.02.2016, p. 203-210.

Research output: Contribution to journalArticle

Castro, Myrella L. ; Franco, Gilson C.N. ; Branco-De-almeida, Luciana S. ; Anbinder, Ana L. ; Cogo-Müller, Karina ; Cortelli, Sheila C. ; Duarte, Simone ; Saxena, Deepak ; Rosalen, Pedro L. / Downregulation of proteinase-activated receptor-2, interleukin-17, and other proinflammatory genes by subantimicrobial doxycycline dose in a rat periodontitis model. In: Journal of Periodontology. 2016 ; Vol. 87, No. 2. pp. 203-210.
@article{53cac2237a3d41f2a6480f7051bec7aa,
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: proteinaseactivated receptor-2 (PAR2), tumor necrosis factor (TNF)-a, interleukin (IL)-17, and IL-1b. Methods: Male Wistar rats were assigned randomly to the following: 1) control group: no ligatureinduced 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-1b, IL-17, TNF-a, 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-a, and IL-1b 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. Conclusion: 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.",
keywords = "Alveolar bone loss, Doxycycline, PAR-2, Periodontal diseases, Receptor",
author = "Castro, {Myrella L.} and Franco, {Gilson C.N.} and Branco-De-almeida, {Luciana S.} and Anbinder, {Ana L.} and Karina Cogo-M{\"u}ller and Cortelli, {Sheila C.} and Simone Duarte and Deepak Saxena and Rosalen, {Pedro L.}",
year = "2016",
month = "2",
day = "1",
doi = "10.1902/jop.2015.150385",
language = "English (US)",
volume = "87",
pages = "203--210",
journal = "Journal of Periodontology",
issn = "0022-3492",
publisher = "American Academy of Periodontology",
number = "2",

}

TY - JOUR

T1 - Downregulation of proteinase-activated receptor-2, interleukin-17, and other proinflammatory genes by subantimicrobial doxycycline dose in a rat periodontitis model

AU - Castro, Myrella L.

AU - Franco, Gilson C.N.

AU - Branco-De-almeida, Luciana S.

AU - Anbinder, Ana L.

AU - Cogo-Müller, Karina

AU - Cortelli, Sheila C.

AU - Duarte, Simone

AU - Saxena, Deepak

AU - Rosalen, Pedro L.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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: proteinaseactivated receptor-2 (PAR2), tumor necrosis factor (TNF)-a, interleukin (IL)-17, and IL-1b. Methods: Male Wistar rats were assigned randomly to the following: 1) control group: no ligatureinduced 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-1b, IL-17, TNF-a, 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-a, and IL-1b 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. Conclusion: 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.

AB - 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: proteinaseactivated receptor-2 (PAR2), tumor necrosis factor (TNF)-a, interleukin (IL)-17, and IL-1b. Methods: Male Wistar rats were assigned randomly to the following: 1) control group: no ligatureinduced 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-1b, IL-17, TNF-a, 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-a, and IL-1b 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. Conclusion: 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.

KW - Alveolar bone loss

KW - Doxycycline

KW - PAR-2

KW - Periodontal diseases

KW - Receptor

UR - http://www.scopus.com/inward/record.url?scp=84964285610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964285610&partnerID=8YFLogxK

U2 - 10.1902/jop.2015.150385

DO - 10.1902/jop.2015.150385

M3 - Article

C2 - 26430924

AN - SCOPUS:84964285610

VL - 87

SP - 203

EP - 210

JO - Journal of Periodontology

JF - Journal of Periodontology

SN - 0022-3492

IS - 2

ER -