Porphyromonas gingivalis infection enhances Th17 responses for development of atherosclerosis

Objectives

Porphyromonas gingivalis has been shown to associate with the development of atherosclerosis. Recent studies indicate that IL-17-producing T helper 17 (Th17) cells have been correlated with the emergence of atherosclerosis. Therefore, we investigated whether the Th17 cell response and expression of Th17-related molecules, in contrast with Th1- and Treg cells, are enhanced by P. gingivalis-challenge in Apolipoprotein E knockout (ApoE KO) mice.

Design

Five mice were intravenously injected with P. gingivalis three times a week for 3 weeks and killed at 15 weeks of age. The proximal aorta lesion area, flow cytometry analysis and IL-17, IL-10, IFN-γ, and IL-1β levels in splenic cultures, and expression of Th17-related molecules in spleen and hearts were examined.

Results

P. gingivalis-challenge showed notable accumulation of atherosclerotic plaques by Oil Red O-staining in ApoE KO mice. Intracellular cytokine staining revealed that significantly elevated CD4⁺ interleukin (IL)-17A⁺ T cells and slightly increased CD4⁺ Foxp3⁺ T cells was recognized in spleen cells of P. gingivalis-challenged mice compared with those from non-infected mice. P. gingivalis-challenge significantly increased IL-17 and IL-1β production and RORγt expression in splenic cells. Furthermore, the expression of Th17-related genes such as IL-6, TGF-β, RORγt and STAT3 were elevated in splenic cells as well as heart tissue of P. gingivalis-challenged mice.

Conclusion

These results suggest that P. gingivalis infection may enhance pro-inflammatory Th17 cell responses in lesion areas and spleen, thereby accelerating atherosclerosis.     

The expression of MCP-1 and CCR2 in induced rats periapical lesions

Objective

Monocyte chemotatic protein-1 (MCP-1) has been found to promote chemotaxis, differentiation, and activation of osteoclasts. The aim of this study is to detect and localize the expressions of MCP-1 and its receptor CCR2 in a rat model of apical periodontitis.

Design

After exposing the pulp of the first mandibular molars, 25 Wistar rats were killed on days 0, 7, 14, 21, 28, and 35. Rat jaws containing the first molar were obtained and routinely prepared for histological analysis, immunohistochemistry, enzyme histochemistry and immunofluorescence staining.

Results

Lesions expanded from day 0 to day 28, and stabilized thereafter. Most of the MCP-1-positive cells were inflammatory cells, and their amount increased from day 7 to day 28. Aside from inflammatory cells, CCR2 was also detected in osteoclasts in the lesions. From day 7 to day 14, the number of osteoclasts increased. From day 21 to day 35, fewer osteoclasts could be observed, and the number of osteoclast was negatively correlated with positive MCP-1 expression.

Conclusion

These findings showed that MCP-1/CCR2 could be observed and might possibly be involved in the development of periapical lesions.     

Histochemical Localization of Dickkopf-1 in Induced Rat Periapical Lesions

Introduction

The purpose of this study was to evaluate the expression of Dickkopf-1 (DKK-1), a secreted antagonist of the Wnt (wingless)/beta-catenin signaling pathway, during the development of periapical lesions in rats.

Methods

Periapical lesions were induced in Wistar rats by occlusal exposure of the pulp of their mandibular first molars. The animals were sacrificed randomly at 0, 7, 14, 21, and 28 day after pulpal exposure. Jaws containing the first molar were obtained and routinely prepared for histologic, immunohistochemical, and enzyme histochemical double immunofluorescence analyses. Data were analyzed using 1-way analysis of variance and Pearson correlation test.

Results

The expansion of the area of periapical lesions was visible from days 7–21 and slowed down thereafter. A few DKK-1- and receptor activator of nuclear factor kappa B ligand (RANKL)-positive cells and osteoclasts were observed on day 7. All positive samples peaked in number on day 14. The expression levels of DKK-1 and RANKL and the number of osteoclasts decreased on days 21 and 28. DKK-1 expression was positively correlated with RANKL expression and osteoclast number from days 7–28.

Conclusions

DKK-1 expression was up-regulated during periapical lesion development. DKK-1 may be associated with the inflammatory response and bone resorption in periapical lesions.     

Kinetics of Th17‐related cytokine expression in experimentally induced rat periapical lesions

Th17‐related cytokines are essential factors in various pathological states, including inflammatory bone destruction. This study investigated the contribution of Th17‐related cytokines to the progress of experimentally induced rat periapical lesions. Periapical pathoses were induced by unsealed exposure of the pulp chamber of the lower first molars. A variety of immunocompetent cells, including CD68⁺ macrophages, Ia antigen⁺ cells and TCRαβ⁺ T cells, were observed in the lesions. The expression levels of Th17‐related cytokines, IL‐17 and IL‐23, and of pro‐inflammatory cytokines, IL‐1β and IL‐6, were significantly increased at 14 days (expansion stage) compared with normal periapical tissues. The expression levels of Foxp3, a regulatory T cell (Treg)‐related gene, and of IL‐10, an anti‐inflammatory cytokine, were higher at 28 days (chronic stage) than at 14 days. These findings suggest that Th17‐related cytokines may be primary contributors to the initiation of periapical bone destruction, and that lesion expansion may be regulated by anti‐inflammatory mediators.     

Mesenchymal Stem Cells as Active Prohealing and Immunosuppressive Agents in Periapical Environment: Evidence from Human and Experimental Periapical Lesions

Introduction

Previous studies describe contrasting molecular profiles of active and inactive periapical granulomas characterized by distinct expression of cytokines, osteoclastogenic factors, and wound healing markers. Although the molecular mechanisms underlying such a dichotomy remain unknown, in this study we investigated the potential involvement of mesenchymal stem cells (MSCs) in determining human and murine periapical lesion activity and outcomes.

Methods

Periapical granulomas (n = 83) and control samples (n = 24) were comparatively assessed for the expression levels of 11 mesenchymal stem cell (MSC) markers using real-time polymerase chain reaction. Experimental periapical lesions induced in mice were evaluated for MSC marker expression and the effects of AMD3100 treatment on lesion outcomes.

Results

MCS marker expression was prevalent in periapical granulomas compared with that in controls, whereas CD29, CD73, CD90, CD146, CD166, NANOG, Stro-1, and CXCR4 expressions were higher in inactive than in active lesions. Experimental periapical lesion inactivity was also associated with an increased expression of MSC markers. The inhibition of MSC mobilization to the periapex by AMD3100 resulted in increased lesion sizes; decreased expression of MSCs and wound healing markers; and increased expression of interleukin 1 beta (IL-17β), interleukin 17 (IL-17), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and nuclear factor kappa-B ligand (RANKL).

Conclusions

Our results show that MSC markers are overexpressed in inactive human and experimental periapical lesions and that MSC mobilization results in the attenuation of experimental lesion progression associated with immunosuppressive and prohealing mechanisms.     

Association of matrix metalloproteinase inducer (EMMPRIN) with the expression of matrix metalloproteinases-1, -2 and -9 during periapical lesion development

Objective

To evaluate the expression of matrix metalloproteinase inducer (EMMPRIN) and its correlation with the expression of matrix metalloproteinases (MMPs)-1, -2 and -9 during the development of periapical lesion in mice.

Methods

Periapical lesions were induced in the lower first molars of mice and after 7, 14, 21 and 42 days the mandibles were removed. The periapical lesions were measured by micro-computed tomography. The expression of EMMPRIN, MMPs-1, -2, and -9 genes were determined by real-time RT-PCR. The location and expression of EMMPRIN and MMPs were evaluated by immunohistochemistry.

Results

At 14 days, the periapical lesion area was higher than at 7 days. At 21 and 42 days no statistically significant bone loss was observed in comparison to 14 days. The control group showed discrete and occasional EMMPRIM, MMP-1, -2 and -9 immunostaining in the periodontal ligament fibroblasts. At 7, 14, 21 and 42 days intense immunoexpression was observed for EMMPRIN, MMPs-1, -2 and -9 in the region adjacent to the apical foramen. The EMMPRIN immunoexpression was higher at 7, 14, 21 and 42 days compared with the control. There was a positive correlation between gene expression of EMMPRIN and MMPs in the active phase of periapical lesion development.

Conclusion

There is a high expression of EMMPRIM mainly by the inflammatory infiltrate in the region adjacent to the apical foramen during periapical lesion development. Furthermore, the positive correlation with MMP-1, -2, and -9 during the first days after periapical lesion induction indicates that EMMPRIM may be involved in the active phase of periapical lesions development.     

Histologic Evaluation of the Effects of Emdogain Gel on Injured Root Apex in Rats

Introduction

This study investigated the effects of Emdogain gel (EMD) on the injured open apex within periapical lesions.

Methods

Periapical lesions were induced in rats by opening the pulp chambers of the mandibular first molars and filing the apical foramen through the distal root canal with #25 K-files to make an open apex. The teeth were exposed to the oral environment for 7 days. Then we irrigated the distal root canals and divided them into EMD-treated and propylene glycol alginate–treated groups. The rats were killed 7, 14, and 28 days after treatment and examined histochemically.

Results

In the EMD-treated rats, more cells expressed transforming growth factor-β1 or bone morphogenetic protein-2 at 7 days after treatment, and the regeneration of cementum and bone was observed around the root apex at 14 days after treatment. Conversely, in the propylene glycol alginate–treated group, few cells expressed transforming growth factor-β1 or bone morphogenetic protein-2, and apical periodontal tissue recovery was rarely seen within the periapical lesions throughout the experiment.

Conclusions

These results suggest that EMD does not irritate injured periapical tissue and may create a favorable environment that promotes the healing of destroyed periapical tissues.     

Distribution of Mast Cells and Macrophages and Expression of Interleukin-6 in Periapical Cysts

Introduction

Mast cells and macrophages are important components of the inflammatory infiltrate found in inflammatory periapical diseases. Several cytokines participate in the mechanisms of inflammation, tissue repair, and bone resorption associated with periapical cysts. The aim of the present study was to evaluate the distribution of mast cells and macrophages and the expression of interleukin-6 (IL-6) in periapical cysts.

Methods

Thirty periapical cysts were selected for the study, and clinical, demographic, and gross information from the cases was obtained from the laboratory records. Five-micrometer sections stained with hematoxylin-eosin were reviewed for analysis of the microscopic features of the cysts, and 3-μm sections on silanized slides were used for immunohistochemical reactions with anti-tryptase, anti-CD68, and anti–IL-6.

Results

There was no statistically significant difference in the mean number of mast cells and macrophages when comparing superficial and deep regions of the fibrous capsule of the cysts. Mean number of mast cells on the superficial region of the fibrous capsule was higher in cysts showing intense superficial inflammation and exocytosis. Macrophages were more commonly found in areas showing IL-6 expression, and IL-6 was less expressed in deep regions of the fibrous capsule in cysts showing greater gross volume.

Conclusions

The results reinforced the participation of mast cells and macrophages in the pathogenesis of periapical cysts and suggested that IL-6 is not the major bone resorption mediator in larger periapical cysts.     

Regulatory T Cells in Mouse Periapical Lesions

IntroductionT-regulatory (Treg, CD4+ FOXP3+) cells constitute a unique subpopulation of CD4+ T cells that inhibit T-cell responses and prevent disease development/exacerbation in models of autoimmunity. In the present study, we tested the hypothesis that Treg cells are induced in periapical lesions by dental pulp infection.MethodsIn situ hybridization (ISH) was used to localize FOXP3+ cells on day 21 after pulp exposure of the first molar teeth and infection with bacteria from the oral environment. FOXP3/GFP knock-in transgenic mice were used to quantify FOXP3+ Treg cells that infiltrate into periapical lesions by flow cytometry on days 7, 14, and 21 after infection. Periodontal ligament from uninfected teeth served as a negative control.ResultsISH showed strong signals that showed the presence of FOXP3+ cells mainly at the periphery of periapical lesions. In contrast, no positive cells were present in the periodontal ligament of uninfected controls. Flow cytometry showed an increase in the number of FOXP3+ Treg beginning between day 7 and day 14 (0.69% of the infiltrate) after infection and increased to day 21 (0.94%) (p < 0.05 and p < 0.001, respectively, vs uninfected controls). Treg were also increased in number in draining cervical lymph nodes after pulpal infection.ConclusionsThese results show that Treg cells are induced to infiltrate into periapical lesions by pulpal infection and suggest that they increase in a time-dependent manner.     

Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh,Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status

Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators'' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas.

Methods

The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas.

Results

The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-γ, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05). Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-γ, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05).

Conclusion

There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic lesions, hierarchical cluster analysis demonstrates the association of TNF-α, IL-21, IL-17 and IFN-γ with lesions activity, and the association of FOXP3, IL-10, IL-9, IL-4 and IL-22 with lesions inactivity.     

8-Year Follow-up of Central Giant Cell Lesion Mimicking Apical Periodontitis

Introduction

Lesions of nonendodontic origin may mimic apical periodontitis. Central giant cell lesions (CGCLs) are aggressive or nonaggressive benign idiopathic intraosseous lesions of the jaw. This report describes a case of a CGCL in the periapical region of teeth #21–#26 of a 17-year-old female who sought orthodontic care because of a change in the position of tooth #23.

Methods

Clinical examination revealed mild facial asymmetry caused by increased volume in the mental region and cortical bone expansion but no cortical disruption. A panoramic radiograph showed a well-defined radiolucent osteolytic lesion involving teeth #21–#26. The cortical bone was not affected, and there was no root resorption. Incisional biopsy was performed, and the diagnosis was a CGCL. The lesion was enucleated surgically. CGCLs should be included in the differential diagnosis of jaw lesions that mimic apical periodontitis.

Results

The patient subsequently underwent orthodontic treatment successfully.

Conclusions

The 8-year clinical and radiographic follow-up confirmed lesion remission, no recurrence, and pulp vitality of all teeth.     

T lymphocyte activation and cytokine expression in periapical granulomas and radicular cysts

Introduction

Radicular cysts (RCs) are periapical lesions resulting in jaw bone destruction. The inflammatory dental periapical granuloma (PG) is considered to be the origin of RC formation; however the mechanism of RC development remains unclear.

Methods

Cell suspension from the surgically extirpated tissue of 27 RCs and 25 PGs was obtained. Bacteriological analysis of the PG tissue samples was performed in order to define two major groups of PG according to the prevailing causative bacterial infection: the streptococcal PG (PG-S, n = 10) and the anaerobe PG (PG-A, n = 9) group. The inflammatory response of tissue infiltrating lymphocytes was assessed by following T lymphocyte activation (HLA-DR expression) as well as interferon γ (IFN-γ) and interleukin 4 (IL-4) production which were evaluated by the flow cytometry.

Results

In comparison to RC both types of PG contained a higher proportion of activated T cells (HLA-DR) and lower proportion of IL-4 producing cells. PG-A tissue contained increased percentage of CD3 cells and increased percentage of T helper 1 (Th1) cells in comparison with PG-S. In RC the IFN-γ production is higher than in streptococcal PG-S but similar as in PG-A.

Discussion

Tissue infiltration by Th2 cells and IL-4 production is likely to play an etiopathogenic role in RC formation.     

Nonendodontic Lesions Misdiagnosed as Apical Periodontitis Lesions: Series of Case Reports and Review of Literature

Introduction

This study aimed to analyze cases referred from a reference service in oral pathology that were initially misdiagnosed as periapical lesions of endodontic origin and to perform a review of the literature regarding lesions located in the apical area of teeth with a nonendodontic source.

Methods

A survey was made of clinical cases derived from the service of oral pathology from 2002 to 2012. The pertinent literature was also reviewed using ScienceDirect and PubMed databases. The lesions were grouped into benign lesions mimicking endodontic periapical lesions (BLMEPLs), malignant lesions mimicking endodontic periapical lesions (MLMEPLs), and Stafne bone cavities. The clinical presentations were divided into lesions with swelling without pain, lesions with swelling and pain, and lesions without swelling but presenting with pain.

Results

The results showed that 66% (37/56) of cases represented benign lesions, 29% (16/56) malignant lesions, and 5% (3/56) Stafne bone cavities. The most commonly reported BLMEPLs were ameloblastomas (21%) followed by nasopalatine duct cysts (13.5%). The most frequently cited MLMEPLs were metastatic injuries (31.5%) followed by carcinomas (25%). The main clinical presentation of BLMEPLs was pain, whereas that of MLMEPLs was swelling associated with pain; Stafne bone cavities displayed particular clinical findings.

Conclusions

Clinical and radiologic aspects as well as the analysis of the patients' medical history, pulp vitality tests, and aspiration are essential tools for developing a correct diagnosis of periapical lesions of endodontic origin. However, if the instruments mentioned earlier indicate a lesion of nonendodontic origin, a biopsy and subsequent histopathological analysis are mandatory.     

The Dynamics of Periapical Lesions in Endodontically Treated Teeth That Are Left without Intervention: A Longitudinal Study

Introduction

The long-term dynamics of periapical lesions in endodontically treated teeth is not fully elucidated, thus presenting a clinical dilemma regarding the need for an intervention. The aim of the study was to retrospectively evaluate the long-term dynamics of periapical lesions that were left without intervention in endodontically treated teeth.

Methods

Periapical status surveys of patients treated in a public dental clinic were retrospectively evaluated for the presence of periapical lesions in endodontically treated coronally restored teeth. The dynamics of the included periapical lesions was evaluated based on the periapical index (PAI) score changes between 2 consecutive periapical surveys of at least a 4-year interval. The influence of various factors on lesion dynamics was statistically evaluated.

Results

The study cohort consisted of 74 patients with a total of 200 endodontically treated teeth having periapical lesions that fulfilled the inclusion criteria. Fifty-seven (28.5%) lesions remained unchanged, 103 (51.5%) lesions worsened (PAI score increased), and 40 (20%) lesions improved (PAI score decreased). Poor root canal filling and poor restoration were found to adversely affect the long-term dynamics of the periapical lesions (P < .05). Age, sex, and the presence of a post had no statistically significant influence on lesion dynamics (P > .05).

Conclusions

Poor root canal filling and poor restoration may adversely affect the long-term dynamics of periapical lesions that are left without intervention in endodontically treated teeth. Therefore, in cases of poor root canal filling or poor restoration, further intervention may be indicated.     

Mineral Trioxide Aggregate as Apical Plug in Teeth with Necrotic Pulp and Immature Apices: A 10-year Case Series

Introduction

This 10-year study evaluated the clinical and radiologic outcomes of teeth with necrotic pulp, immature apices, and periapical lesions treated with the mineral trioxide aggregate (MTA) apical plug technique.

Methods

Seventeen single-rooted immature teeth with necrotic pulp and periapical lesion from 17 patients treated between January 2001 and December 2001 were included in this study. Apical obturation on all teeth included in the study was completed in 2 visits: first using calcium hydroxide as an interappointment intracanal medication and a second visit for the creation of the artificial apical barrier with MTA. The outcome, based on clinical and radiographic criteria, was assessed by 2 calibrated investigators using the periapical index (PAI). The Friedman test was used to verify the differences between baseline and the 1-, 5-, and 10-year PAI scores.

Results

Of the 17 patients treated, 1 patient dropped out at 5 years. At the 10-year follow-up, 15 teeth were healed (PAI ≤2), and 1 tooth had been extracted because of the presence of a longitudinal root fracture. The PAI score exhibited a significant decrease between baseline and 1 year and between 1 and 5 years. The difference between 5 and 10 years was not significant.

Conclusions

The apical plug with MTA was a successful and effective technique for long-term management of this group of teeth with necrotic pulps with immature root development and periapical lesions.     

调节性T细胞和Th17细胞在OLP中的表达

目的：通过观察调节性T细胞（regulatory Tcells,Treg）和Thl7细胞（helper Tcells17,Th17）在口腔扁平苔藓（OLP）组织中的表达情况,探讨其在OLP发生发展过程中的变化。方法：应用免疫组织化学双标记技术检测35例OLP患者和19例对照组口腔黏膜组织中CD25＋Foxp3＋、CD4＋IL-17＋细胞的表达。结果：OLP组病损组织中有大量CD25＋Foxp3＋细胞浸润,较对照组显著增多,两者差异非常显著（P〈0．01）。CD4＋IL-17＋细胞在OLP组织中的表达较正常口腔黏膜组织有增加趋势,但差异无统计学意义（P〉0．05）。经进一步统计学分析,CD25＋Foxp3＋细胞和CD4＋IL-17＋细胞数量改变在OLP组织中表达呈正相关（P〈0．05）。结论：Treg细胞的数量在OLP组织中增多,Thl7细胞可能协同Treg细胞,在OLP发生发展过程中发挥了一定的作用。     

Incidence of Cholesterol in Periapical Biopsies among Adolescent and Elderly Patients

Introduction

Cholesterol clefts are common histologic findings in periapical biopsies; they have a reported incidence in periapical periodontitis of up to 44%. Cholesterol crystals are also recognized in advanced atherosclerotic plaques in humans. Male sex, genetic abnormalities, and age have been associated with advanced atherosclerotic lesions. Among these nonmodifiable risk factors, age is the most dominant. The aim of the study was to evaluate if age is also linked to cholesterol deposition in periapical periodontitis.

Methods

The database of biopsy reports obtained between 2006 and 2009 was searched for specimens diagnosed as radicular cysts or periapical granulomas. Only data relating to biopsies obtained from adolescent (13–21 years old) and elderly (over 60 years old) patients were selected. The biopsies were examined by a pathologist under a light microscope (Zeiss, Jena, Germany) at magnifications of 40×–200×. The available material was scanned for the presence of cholesterol clefts and foamy cells in radicular cysts and granulomas.

Results

A total of 41 specimens were collected in the adolescent group and 48 specimens in the elderly group over a 4-year period. A higher incidence of cholesterol was found in the elderly group compared with that in the adolescent group (odds ratio = 6.857).

Conclusions

The highly significant incidence of cholesterol deposits in periapical biopsies among elderly patients may be a possible cause for the lack of repair. The mechanism for cholesterol accumulation is probably similar to the process leading to atherosclerosis and coronary artery disease. Statin administration may be advantageous for the treatment of persistent lesions. A clinician should be aware of the risk for persistent lesions after endodontic treatment in elderly patients.     

Higher Expression of Galectin-3 and Galectin-9 in Periapical Granulomas than in Radicular Cysts and an Increased Toll-like Receptor-2 and Toll-like Receptor-4 Expression Are Associated with Reactivation of Periapical Inflammation

Introduction

Cysts and periapical granulomas are inflammatory reactions that develop in response to periapical infection by microbial species in dental root canal. It is known that toll-like receptors (TLRs) are pathogen recognition molecules and that galectins are lectins that can be associated with the inflammatory process, stimulating or inhibiting the immune system. The objective of this study was to evaluate the in situ expression of TLRs and galectins in radicular cysts and periapical granulomas.

Methods

We analyzed 62 cases (30 radicular cysts, 27 periapical granulomas, and 5 control cases). Indirect immunohistochemistry was used to evaluate the expression of TLRs (TRL-2 and TLR-4) and galectins (Gal-3 and Gal-9).

Results

The expression of Gal-3 and Gal-9 was significantly higher in periapical granulomas and radicular cysts than in the control group. Similarly, both Gal-3 and Gal-9 were expressed significantly more in periapical granulomas than in radicular cysts. The expression of TLR-2 was significantly higher in periapical granulomas and radicular cysts than in the control group, and it was also significantly higher in radicular cysts with sinus tract than in the cases without sinus tract. Furthermore, the expression of TLR-4 was significantly higher in the cases of periapical granulomas with sinus tract than in the cases without sinus tract.

Conclusions

Gal-3/Gal-9 and TLR-2/TLR-4 expression in the periapical granulomas and radicular cysts is associated with reactive periapical inflammation. Pathobiology of periapical disease is a very complex interplay of many bioactive molecules involved in immunoinflammatory responses. Up-regulation of these bioactive molecules might be an important modulator of inflammatory periapical lesions.