CCL5's Role in Periodontal Disease: A Narrative Review.

Persistent host inflammatory and immune responses to biofilm play a critical role in the mechanisms that govern soft and hard tissue destruction in periodontal disease. Among the less explored facets of these mechanisms are chemokines, including CCL5 (C-C motif chemokine ligand 5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), a proinflammatory CC subfamily chemokine synthesized by T lymphocytes. Despite its importance, there is currently no comprehensive review of the role of CCL5 in periodontitis in the literature. Therefore, this paper aims to fill this gap by summarizing the existing knowledge on the involvement of CCL5 in the onset and progression of periodontitis. In addition, we aim to stimulate interest in this relatively overlooked factor among periodontitis researchers, potentially accelerating the development of drugs targeting CCL5 or its receptors. The review examines the association of CCL5 with periodontitis risk factors, including aging, cigarette smoking, diabetes, and obesity. It discusses the involvement of CCL5 in pathological processes during periodontitis, such as connective tissue and bone destruction. The data show that CCL5 expression is observed in affected gums and gingival crevicular fluid of periodontitis patients, with bacterial activity contributing significantly to this increase, but the reviewed studies of the association between CCL5 expression and periodontal disease have yielded inconclusive results. Although CCL5 has been implicated in the pathomechanism of periodontitis, a comprehensive understanding of its molecular mechanisms and significance remains elusive, hindering the development of drugs targeting this chemokine or its receptors.

The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland.

OBJECTIVES: Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors. DESIGN: The study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer. RESULTS: Pleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD. CONCLUSIONS: Summarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma.

The role of Nrf2 in pathology of pleomorphic adenoma in parotid gland.

BACKGROUND: Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, the processes involved in its carcinogenesis are not well defined. This study aimed to define the contribution of Nfr2 (nuclear factor (erythroid-derived 2)-like 2) to pleomorphic adenoma pathology. The Nrf2-controlled gene system is one of the most critical cytoprotective mechanisms, providing antioxidant responses. MATERIAL AND METHODS: The study was carried out in pleomorphic adenoma and control parotid gland tissues, investigating gene expression of NFE2L2, as well as KEAP1 (Kelch-like ECH-associated protein 1) and NQO1 (quinone oxidoreductase), at mRNA and protein (immunohistochemistry) levels. Functional evaluation of Nrf2 system in the parotid gland was evaluated in HSY cells (human parotid gland adenocarcinoma cells). RESULTS: Pleomorphic adenoma specimens showed cytoplasmic and nuclear Nfr2 expression in epithelial cells, as well as more variable lower Nrf2 level in mesenchymal cells. In the parotid gland, Nrf2 was expressed in cytoplasm of serous, mucous, and duct cells. Nuclear Nrf2 expression was predominantly seen in serous cells, whereas mucous and duct cells were mostly negative. Comparable mRNA levels of NFE2L2 and NQO1 genes and significantly higher expression of KEAP1 in pleomorphic adenoma were seen. HSY cell incubation with oltipraz demonstrated significant elevation of NFE2L2 after 24 and 48 hours of stimulation, whereas NQO1 was elevated, but significantly only after 24 hours, and KEAP1 expression remained unchanged. CONCLUSIONS: Summarizing both in vitro and in vivo observations, it can be stated that Nrf2 may play a role in the pathology of pleomorphic adenoma.

Expression and functional regulation of the nuclear receptors AHR, PXR, and CAR, and the transcription factor Nrf2 in rat parotid gland.

Nuclear receptors and transcription factors regulate the functions of many genes involved in cellular physiology and pathology (e.g. tumorigenesis and autoimmune diseases). The present study was performed to define the expression and the regulation of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), and nuclear factor E2-related factor 2 (Nrf2) in the rat parotid gland. Constitutive expression, as well as expression after stimulation with specific inducers for AhR [2,3,7,8-tetrachloro-dibenzylo-p-dioxin (TCDD)], Nrf2(oltipraz), PXR (dexamethasone), and CAR (phenobarbital), was evaluated using the quantitative PCR. Cellular localization of the nuclear receptors and the transcription factor was visualized by immunohistochemical staining. The study revealed constitutive expression of AhR as well as Nrf2, and their induction by TCDD andoltipraz, respectively. Immunohistochemical analysis revealed constitutive, predominantly cytoplasmic, expression of the AhR receptor, especially in interlobular striated duct cells, with nuclear shift upon exposure to TCDD. Inducible expression of Nfr2 was found mainly in the cytoplasm of intralobular striated duct cells. Constitutive expression of PXR and CAR was not found. Bearing in mind the involvement of AhR and Nrf2 in the regulation of many genes, it seems that these factors may play also a role in salivary gland physiology and pathology.

IL-1 and TNF-α regulation of aryl hydrocarbon receptor (AhR) expression in HSY human salivary cells.

OBJECTIVES: Recent findings demonstrate that nuclear receptor - aryl hydrocarbon receptor (AhR) may play an important role in the pathogenesis of Sjögren's syndrome (SS) via involvement in Epstein-Barr virus reactivation. In that study a reporter system was used. Therefore, it was decided to define AhR expression in human salivary cell line (HSY) and its functional regulators. DESIGN: The expression and functional regulation of AhR was studied in HSY cells. The cells were incubated with dioxin (TCDD) - AhR model inducer, IL-1 and TNF-α. qRT-PCR was applied to assess the expression of AHR, AHRR (AhR repressor), ARNT (AhR nuclear translocator) as well as AhR dependent genes: CYP1A1 and CYP1B1. Enzymatic activity of CYP1A1 and CYP1B1 was evaluated using luciferin-labelled CYPs substrate. RESULTS: In general, dioxin did not significantly influence the expression of AHR and ARNT, but reduced AHRR level. AhR dependent gene expression, i.e. CYP1A1 and CYP1B1 increased gradually with TCDD incubation time. TNF-α significantly induced AHR along with CYP1A1 and CYP1B1 expression. IL-1ß did not affect AHR expression, and had minimal effects on CYP1 mRNA levels. Exposure of HSY cells to TCDD resulted in time-dependent induction of CYP1A1 and CYP1B1 enzymatic activity. CONCLUSIONS: This study documents functional expression of AhR in HSY as well as induction of AhR and its dependent genes by TNF-α.

Effect of different water flows on root surface temperature during ultrasonic removal of posts.

OBJECTIVE: This in vitro study evaluated rises in temperature on the outer root surface of human incisors during ultrasonic post removal with different water flows. STUDY DESIGN: Thirty-six extracted teeth (12 maxillary central incisors, 12 maxillary lateral incisors, and 12 mandibular incisors) were used. After root canal preparation, the teeth were obturated, and prefabricated posts were cemented into the prepared spaces. Posts were ultrasonically instrumented dry and with irrigation at 20 mL/min and 40 mL/min. Temperature changes on the entire mesial outer surfaces of the roots were measured at 10-second intervals using an infrared thermal imaging camera. RESULTS: Increases in root surface temperature were significantly lower when posts were instrumented with 40 mL/min water irrigation compared with dry vibration and 20 mL/min irrigation, which also significantly differed from each other. Statistical analysis among tooth groups showed differences in the mean temperature rise of maxillary central incisors and maxillary lateral incisors compared with mandibular incisors when posts were instrumented dry or with 20 mL/min irrigation. There were no significant differences in mean temperature rises between the studied groups when 40 mL/min irrigation was used. CONCLUSIONS: Water cooling during ultrasonic post instrumentation significantly reduced temperature increases on the outer root surface; however, the intensity of the cooling was also important. Our results suggest that copious water irrigation during post removal is an effective method to protect the root's surrounding tissue.

[The effect of environmental and genetic factors in the pathogenesis of periodontitis]. / Ocena wplywu wybranych czynników srodowiskowych i genetycznych na wystepowanie i stopien intensywnosci zapalen przyzebia.

INTRODUCTION: The pathogenesis ofperiodontitis has not been completely defined, therefore the study was aimed at evaluating combined effects of environmental factors as well as interleukin-1beta (IL-1beta) and FcgammaRIIa genotypes on the risk of periodontal disease. MATERIAL AND METHODS: The study was carried out on 52 patients diagnosed with periodontitis (P), 20 suffering from aggressive periodontitis (AgP), 32 with chronic periodontitis (CP) as well as 52 subjects with healthy periodontium (HP). Interleukin-1beta genotype was evaluated using PCR-RFLP, whereas FcdeltaRIIa polymorphism with the application of PCR-ASA method. RESULTS: The frequency of IL-1beta 1/1, 1/2, 2/2 genotype was as follows: AgP patients--75%, 25%, 0%, CP: 65.6%, 34.4%, 0%, and P: 69.2%, 30.7%, 0%, respectively, and did not differ significantly from HP. Alike, no significant differences were found in FcgammaRIIa genotype distribution. H/H, R/H, R/R genotypes were revealed in 40.0%, 35.0%, 25.0% for AgP, 43.8%, 40.6%, 15.6% in CP patients, 42.3%, 38.5%, 19.2% for P subjects as well as 36.5%, 48.1%, 15.4% in HP subjects. Multivariate analysis revealed a significant association between AgP and age, smoking and API > 50%. As for CP significant association was found solely for API > 50%. CONCLUSIONS: IL-1B(+3954) and FcgammaRIIa (CD32) gene polymorphisms are not associated with an increased risk of AgP and CP.

Subepithelial connective tissue graft in the treatment of multiple gingival recession.

OBJECTIVES: There is a paucity of data on the coverage of multiple recessions. The aim of this study was to compare clinical results of connective tissue graft (CTG) combined with tunnel surgical techniques in the treatment of multiple adjacent gingival recessions. STUDY DESIGN: The treatment outcome of 28 recessions of Miller Class I and 20 recessions of Miller Class II in 18 patients was compared. Clinical evaluation, taken before the surgery as well as 6 and 12 months afterwards, included recession height, recession width, keratinized tissue width, and probing depth. RESULTS: No differences of recession coverage comparing recession class I and recession class II were found (mean coverage 99.1% and 98.9%, respectively). Twelve months after surgery, 79.2% of recession class I and 72.2% of recession class II were entirely covered. CONCLUSIONS: Surgical treatment of multiple recessions using CTG in combination with the tunnel technique resulted in significant root coverage of both class I and class II recessions, and increased keratinized gingival width.