Expression of 5-Lipoxygenase and Cyclooxygenase-2 during Apical Periodontitis Development

Objectives: Apical periodontitis is an inflammatory diasease caused by microorganisms invading dental root canal. Although the role of several inflammatory mediators has been established in apical periodontitis progression, the expression of enzymes involved in aracdonic acid metabolism has not been characterized. Therefore the purpose of this investigation was to evaluate the kinetics of expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) during apical periodontitis development in mice.

Methods:  Apical periodontitis was experimentally induced in the first molar of C57BL/6 (n=24), 5-LO^-/- knockout (129-Alox5^tm1Fun; n=24) and strain-matched wild-type (n=24) mice using E. coli lipopolysaccharide (LPS; 0.1 and 1mg/ml). Animals were euthanized at 7, 14, 21 and 28 days following root canal contamination and tissues were removed for histological evaluation and RNA extraction. COX-2 and 5-LO mRNA expression was evaluated by qRT-PCR. Data was analysed using one-way ANOVA followed by Tukey test (α=0.05).

Results: 0.1 or 1mg/ml of LPS induced apical periodontitis which was characterized by infiltration of inflammatory cells in periapical area and bone resorption. The intensity of inflammation and bone resorption was dose and time dependent. COX-2 and 5-LO mRNA expression increased following root canal contamination and reached higher expression at 7 days for 5-LO (p<0.05) and 14 days for COX-2 (p<0.05). After that, COX-2 mRNA expression decreased to baseline (p>0.05) whereas 5-LO expression remained slightly higher than baseline (p<0.05). COX-2 mRNA expression was higher in 129-Alox5^tm1Fun and wild-type mice compared to C57BL/6 mice while 5-LO mRNA expression was higher in C57BL/6 compared to wild-type mice. 5-LO mRNA was not detected in 129-Alox5^tm1Fun mice.

Conclusions: COX-2 and 5-LO mRNA were detected in apical periodontitis, mainly in earlier periods following root canal contamination. These findings indicate that COX-2 and 5-LO might be important for inflammatory cell recruitment and bone resorption in apical periodontitis.

Financial support: FAPESP and CAPES.