Antimicrobial Mouthwashes: An Overview of Mechanisms-What Do We Still Need to Know?

This narrative literature review is the first in a 6-section supplement on the role of mouthwashes in oral care. This introduction briefly summarises current knowledge on antimicrobial mechanisms, relating to some of the most common over-the-counter mouthwash products available worldwide: chlorhexidine, hydrogen peroxide, cetylpyridinium chloride, povidone iodine, and essential oils. The aim of this first article is to describe how mouthwashes "kill" pathogenic microbes when used adjunctively and thus provide a basis for their widespread use to manage key oral diseases, namely caries, gingivitis, and periodontal disease. This article therefore sets the scene for subsequent, more detailed exploration of mouthwashes regarding their clinical effectiveness, impact on the oral microbiome, and possible effects on systemic health as well as natural alternatives and future directions. Other than the clinical effectiveness (for certain agents) of mouthwashes, on many topics there remains insufficient evidence for systematic review or formulation of robust national guidelines. The supplement, therefore, compiled by an international task team, is aimed at general dental practitioners across the globe, as an easy-to-read guide for helping to advise patients on mouthwash use based on the current best available evidence.

The modification of meteorological factors on the relationship between air pollution and periodontal diseases: an exploration based on different interaction strategies.

We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.

Chemotherapy as a risk factor for caries and gingivitis in children with acute lymphoblastic leukemia: A retrospective cohort study.

BACKGROUND: Dental and oral anomalies are among the most common long-term side effects of childhood cancer therapy. AIM: To evaluate chemotherapy as a risk factor for caries lesions and gingivitis in children with acute lymphoblastic leukemia (ALL) treated with the ALL IC-BFM 2009 chemotherapy protocol. DESIGN: A retrospective cohort study was designed. Clinical records of 23 paediatric patients with ALL exposed to chemotherapy in the Regional Hospital in Valdivia, Chile, and 46 unexposed patients assessed every 3 months for 24 months were analyzed. The data on gender, age, index of the number of decayed, missing, or filled teeth, and the presence of gingivitis were recorded (Mann-Whitney U test and logistic regression analysis, p ≤ .05). RESULTS: A significantly greater frequency of gingivitis (69.57%; p < .002) and a mean of new caries lesions were observed in children treated with chemotherapy than in the unexposed children (p < .01). The chemotherapy protocol presented a relative risk of 2.15 (95% CI = 1.22 - 2.66; p = .01) for new caries lesions and 2.29 (95% CI = 1.76 - 3.82; p = .002) for gingivitis. CONCLUSION: The ALL IC-BFM 2009 chemotherapy protocol in patients with ALL is a risk factor for new caries lesions and gingivitis.

The Effect of Porphyromonas gingivalis Lipopolysaccharide on the Pyroptosis of Gingival Fibroblasts.

Periodontitis is a chronic inflammatory disease induced by Porphyromonas gingivalis (P. gingivalis) and other pathogens. P. gingivalis release various virulence factors including lipopolysaccharide (LPS). However, whether P. gingivalis-LPS inducing pyroptosis in human gingival fibroblasts (HGFs) remains unknown. In present study, P. gingivalis-LPS decreased the membrane integrity of HGFs, and pyroptosis-associated cytokines were upregulated at the mRNA level. In addition, pyroptosis proteins were highly expressed in gingival tissues of periodontitis. P. gingivalis-LPS induced gingivitis in the rat model, and the expression level of pyroptosis-associated proteins increased. Together, P. gingivalis-LPS can activate the pyroptosis reaction, which may be a pro-pyroptosis status in a relative low concentration.

Severe erosive gingivostomatitis in a patient treated by vedolizumab.

Vedolizumab is a humanized monoclonal antibody that binds to the human a4ß7 integrin and is approved for use in inflammatory bowel diseases. We describe a patient with severe, refractory erosive gingivostomatitis, which appeared a few days after the first dose of vedolizumab and resolved after discontinuation of the drug. We believe the gingivostomatitis to be a direct side effect of vedolizumab, rather than an extraintestinal manifestation of the underlying inflammatory bowel diseases. The clinicians need to be aware of this adverse event, which could be mistakenly considered as an extraintestinal manifestation of inflammatory bowel diseases.

Bleeding Index and Monocyte Chemoattractant Protein 1 as Gingival Inflammation Parameters after Chemical-Mechanical Retraction Procedure.

OBJECTIVE: A widely used chemical-mechanical method of gingival retraction can cause gingival tissue damage. The aim of this study was to test the influence of the chemical-mechanical gingival retraction procedures on the gingival bleeding index (GBI) and the salivary concentration of monocyte chemoattractant protein 1 (MCP-1) as an indicator of inflammatory changes in the gingiva. MATERIALS AND METHODS: The effects of 2 different retraction agents (aluminum chloride and ferric sulfate) were compared, particularly their tissue damaging effect during tooth preparation. Therefore, GBI values and the salivary concentration of MCP-1 were assessed during the chemical-mechanical method of gingival retraction in a homogenous group of respondents. The subjects (n = 60) were divided into 2 experimental groups (G1 and G2) regarding the need for tooth preparing and making artificial crowns. Each group was further divided into 2 subgroups (R1 and R2) according to the type of the gingival retraction agent used (aluminum chloride and ferric sulfate). RESULTS: Compared to the values at the study start, a statistically significant increase in GBI and salivary MCP-1 (p < 0.001) 1 day after gingival retraction agent application was observed in both experimental groups. After 72 h, the values were lower than in the second observation period but still statistically significantly higher compared to the study start (p < 0.001), which indicated the reversibility of the tissue changes. CONCLUSION: Higher values of the investigated parameters were observed in the group of subjects with prepared teeth, and clinical changes were more pronounced after the use of ferric sulfate.

EFFICACY OF MULTIVITAMINS AND LYSOZYME TABLETS IN COMPLEX MANAGEMENT OF PLAQUE-INDUCED GINGIVITIS IN CHILDREN: A COMPARATIVE BIOCHEMICAL STUDY.

Although the pathogenesis of periodontal lesions has not been sufficiently studied, recent studies show that plaque formation and host immune response are important factors. The purpose of this study was improving efficiency of plaque-induced gingivitis treatment in children with immunological correction of saliva by administration of polyvitamins and lysozyme tablets. We have examined 60 12-year-old children diagnosed with plaque-induced gingivitis and divided them into the main and control groups consisted of 30 children in each accordingly. The children of both groups were treated by sanitation and professional oral hygiene. The children of the main group besides were prescribed with multivitamins complex "Supervit" and tablets "Lizak". The efficiency of the introduced complex we have assessed by contain of immunoglobulins A (IgA), immunoglobulins G (IgG), secretory immunoglobulin A (s-IgA), interleukin 1ß (IL-1ß), interleukin 4 (IL-4) and lysozyme in saliva. After 6 month the treatment children from the main group showed a decline in concentration of IL-1ß by 30,06 % (р<0,01), IgA by 33,34 %, IgG by 12,5 % (р<0,05). The present data support the high efficiency of the introduced treatment that has been proved by positive progress of immunological indexes in saliva taken within six and 12 month since the research.

Impact of oral contraceptives on periodontal health.

BACKGROUND: Oral contraceptives pills (OCPs) are common and a convenient form of contraception. The use of hormonal contraceptives by women has been considered to influence gingival and periodontal disease progression. AIM: This study was conducted to assess the effect of oral contraceptive pills on the periodontal health. MATERIALS AND METHOD: A cross-sectional comparative study was conducted among 200 females aged 18 years and above of Jaipur city. The study subjects were divided into two groups i.e. contraceptive users and non-contraceptive users, each group consisted 100 females. Data was collected using Modified WHO Performa (1997). Periodontal status was examined using Community Periodontal Index (CPI) and Loss of Attachment (LOA). Chi-square test and one sample t-test was used for statistical analysis and P value was set (p< 0.05) as significant. RESULTS: Mean CPI score in subjects and non-contraceptive users was 2.34+ 0.81 and 1.16+ 0.89 respectively. Mean LOA score in each group was 0.28+ 0.45 and 0.19+ 0.50 respectively. CONCLUSION: Oral Contraceptive pills had adverse effects on periodontal health.

Chronic occupational exposure to lead leads to significant mucocutaneous changes in lead factory workers.

BACKGROUND: Chronic lead toxicity is a worldwide public health problem. Lead possesses deleterious effects on many organ systems. However, little is known regarding its clinical and biophysical effects on the skin. OBJECTIVE: To investigate mucocutaneous signs and biophysical property changes in skin after chronic lead toxicity. METHODS: One hundred and eighty-seven patients who were car battery workers participated in the study. Complete history and physical examination were performed. Blood was collected for laboratory analyses. Thorough skin examination by dermatologists was carried out in 134 subjects. Additionally, 96 patients with blood lead levels (BLL) >70 µg/dL were further evaluated for skin elasticity, sebum content, transepidermal water loss (TEWL), hydration, pH and pigmentation. An equal number of age-, sex- and skin-type-matched subjects were recruited as controls. RESULTS: The mean BLL of all subjects was 74.15 ± 11.58 µg/dL. The most frequently observed signs were gingival brown pigmentation in 112 (83.6%), gingivitis in 111 (82.8%) and lead line in 66 (49.3%) patients. The lead line was found in subjects with significantly higher BLLs (adjusted mean difference 6.45, 95% CI 2.30-10.60 µg/dL, P = 0.003) and in association with gingivitis (adjusted OR 7.32, 95% CI 2.08-25.74, P = 0.002). Mean BLL of the patients who underwent biophysical assessment was 82.77 ± 9.80 µg/dL. Patients exhibited a statistically significant lower skin hydration observed by corneometer as well as elasticity. The adjusted ORs of having dry skin and lower elasticity were 15.32 (95% CI 4.41-53.24), P < 0.001) and 1.96 (95% CI 1.06-3.60), P = 0.031), respectively. These differences were not significant for sebum content, TEWL, pH and pigmentation. CONCLUSION: Importantly, even in normal-appearing skin, level of hydration and elasticity decreased in lead-intoxicated patients. These results suggest that lead might possess harmful effects on the skin at measurable levels.

Anti-inflammatory and antioxidative effects of the buds from different species of Populus in human gingival fibroblast cells: Role of bioflavanones.

BACKGROUND: Poplar leaf-buds (Populi gemmae) are used traditionally as anti-inflammatory agents to the treatment of skin injuries or cough. They differ in their diverse chemical composition and different types of activities, whose mechanisms are not fully recognized. PURPOSE: Evaluation and comparison of anti-inflammatory activity of leaf-buds extracts from Populus nigra, P. × berolinensis and P. lasiocarpa and flavanones - pinocembrin and pinostrobin towards human gingival fibroblasts (HGF-1) pro-inflammatory stimulated by silver nanoparticles (AgNPs). Determination of antioxidant activity associated with anti-inflammatory properties by means of bioautographic TLC tests. METHODS: Phytochemical analysis was performed by TLC and videodensitometry analysis. The extracts were standardized on the pinocembrin and pinostrobin content. Bioautography was performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and riboflavin-light blue tetrazolium chloride (riboflavin-light-NBT) radicals to assess the extracts and both flavanones radical scavenging properties as well as potential inhibition of xanthine oxidase (XO) activity. The protective effects of poplar buds extract and flavanones - pinocembrin and pinostrobin on HGF-1 line exposured to AgNPs were investigated by analysis of interleukin 6 (IL-6) and interleukin IL-1ß (IL-1ß) level measured by ELISA kit. The messenger ribonucleic acid (mRNA) of both cytokines was determined by real-time quantitative PCR. The involvement of cyclooxygenase 2 protein (COX-2) was studied using Western blot analysis. RESULTS: The presence of several flavanones and phenolic acids, which have radical scavenging properties, was revealed in all of the bud poplar extracts analyzed. Treatment with particular flavanones or extracts from buds of P. × berolinensis and P. nigra decreased the IL-6 and IL-1ß release in HGF-1 cells and down-regulation of mRNA for both cytokines was observed. The COX-2 protein expression was demonstrated for pinocembrin and P. × berolinensis buds. These effects were not observed for buds from P. lasiocarpa not containing of flavonoids. CONCLUSION: The potential protective role of pinocembrin and pinostrobin and extracts from buds P. nigra and P. × berolinensis against AgNPs induced inflammation and cytotoxicity in HGF-1 cells is disclosed. In addition, the antioxidant properties of poplar bud extracts have been demonstrated. P. × berolinensis buds showed the highest activity in both the in vitro model and in the bioautographic tests.

Impact of the use of Kampo medicine in patients with esophageal cancer during chemotherapy:a clinical trial for oral hygiene and oral condition.

OBJECTIVE: The aim of this study was to investigate the impact of the use of two Kampo medicines on oral mucositis, tongue coating bacteria, and gingiva condition in patients with esophageal cancer undergoing chemotherapy. METHODS: Twenty-three esophageal cancer patients who receive chemotherapy at Tokushima University Hospital, were included. The participants, who received professional oral healthcare, were randomly divided into three groups:7 subjects received Daiokanzoto sherbets, 7 subjects received Hangeshashinto sherbets, and 9 subjects received nothing (control). The numbers of total bacteria and specific periodontopathogenic bacteria in tongue coating were determined in addition to clinical parameters. RESULTS: No difference on the onset of oral mucositis was found among the three groups. However, tongue coating index, gingival index (GI), plaque index, the number of total bacteria, Fusobacterium nucleatum and Campylobacter rectus were decreased during chemotherapy. More specifically, GI as well as the number of F. nucleatum and C. rectus were decreased significantly in the Daiokanzoto group when compared to the control group (psize 8 < 0.05). No such differences were observed for the group receiving Hangeshashinto. CONCLUSION: This clinical trial showed that Daiokanzoto might be effective in attenuating gingival inflammation and reducing the levels of periodontopathogenic bacteria in patients with esophageal cancer. J. Med. Invest. 65:184-190, August, 2018.

[Medicaments and oral healthcare. Adverse effects of medicines and self care products on the gingiva]. / Serie: Medicamenten en mondzorg. Bijwerkingen van medicamenten en zelfzorgmiddelen op de gingiva.

Medications and self care products may have adverse effects on the gingiva. These adverse effects can be divided into inflammation, intrinsic discolouration, irritation, trauma, cytotoxicity, lichenoid reaction, and proliferation. This article deals with the first 6 types of adverse effects mentioned: a subsequent article will deal with the last type mentioned. Since contraceptives were introduced, there have been indications that they cause or promote gingivitis, but with the current contraceptives this adverse effect is rarely seen. Intrinsic discolouration of the gingiva has been reported when using Staloral®, minocycline, contraceptives and hydroxychloroquine. Irritation and trauma of the gingiva are seen when self care products containing carbamide peroxide or hydrogen peroxide are used for external tooth whitening, or which have analgesic potential, such as acetylsalicylic acid and hydrogen peroxide or oral rinses containing alcohol. Several cytostatics may induce apoptosis of keratinocytes in the gingiva. Oral rinses with antibacterial ingredients have cytotoxic potential. Lichenoid reactions have been reported due to the use of several (groups of) medications.

Gingival tissue reaction to direct adhesive restoration: A preliminary study.

INTRODUCTION: It is debated whether composite resin marginal/submarginal direct restoration can be usefully performed without inflammatory consequences. This histological study is the first human analysis aimed to compare, in the same tooth, the gingival tissue close to composite resin restorations with gingival tissue close to hard tissue. METHODS: Eight healthy patients with almost a residual strategic tooth needing endodontic therapy, and post-and-core restoration, then indirect prosthetic restoration, were selected. Direct margin relocation with composite resin was necessary to perform endodontic treatment. The crown lengthening with a secondary flap harvested was necessary to perform prosthetic rehabilitation. Three months after marginal relocation, the secondary flap was harvested, embedded in PMMA, 4-µm sectioned, and stained to analyze the inflammation degree. RESULTS: All patients completed post-and-core reconstruction and the planned prosthetic therapy, maintaining the stringent hygienic protocol plan. The inflammation level comparison, slightly lower in gingiva close to the teeth (3.62 ± 0.38) than in gingiva close to the composite (3.75 ± 0.26), results in a p-value of 0.11 after Wilcoxon test. CONCLUSIONS: Results highlight a minimal, statistically not significant difference in the inflammation degree after margin relocation, conceivably due to patients, teeth and cases selection, together with adopted stringent methodological and supportive measures.

Khat (Catha edulis) and its oral health effects: An updated review.

Khat or qat (Catha edulis) is a plant that grows in East Africa and southern Arabia. The leaves and twigs of this small tree are chewed by several millions of people worldwide for their stimulating amphetamine-like effects. The reported prevalence of khat chewing in Europe and the USA is on the rise, especially with global migration. Long-term khat chewing has several detrimental general and oral health effects. The aim of the present study was to review the current literature regarding khat use and its association with oral and dental diseases, with particular emphasis on its link with oral keratotic white lesions and oral cancer. We searched the literature to identify all relevant articles. Studies showed that khat is associated with several oral and dental conditions, including keratotic white lesions, mucosal pigmentation, periodontal disease, tooth loss, plasma cell stomatitis, and xerostomia. There are limited data on the incidence of dental caries among khat chewers. The evidence that khat chewing is a risk factor for oral cancer is still weak, and is mainly based on anecdotal case reports and uncontrolled studies.

Histological evaluations and inflammatory responses of different dental implant abutment materials: A human histology pilot study.

BACKGROUND: Improvements of soft tissue to the abutment surface results in more stable peri-implant conditions, however, few human histological studies have compared soft tissue responses around different abutment materials. PURPOSE: To describe the peri-implant tissue around 3 abutment materials; titanium, zirconia, and gold alloy, over an 8-week healing period. MATERIALS AND METHODS: Fifteen edentulous sites were treated with implants. Eight weeks later, peri-implant tissue was harvested and processed using a nonseparation resin embedded technique. The tissue attachment characteristics were assessed at clinical stages using the gingival index (GI) score, surgical stage (surgical score), and histological stage (histological attachment percentage). Additionally, the inflammatory responses were evaluated using inflammatory extent and inflammatory cellularity grades. Nonparametrical statistics were used to describe the GI and surgical scores, and analytical statistics were used to analyze the histological attachment percentages as well as the inflammatory extent and cellularity grades amongst the 3 groups. RESULTS: There were no statistically significant differences among the groups for GI score (P = .071) and surgical score (P = .262). Titanium and zirconia exhibited nearly similar mean histological attachment percentages while gold alloy had a significantly lower percentage (P = .004). For the inflammatory extent and cellularity grades, the odds of being one grade higher for gold alloy abutment was 5.18 and 17.8 times that of titanium abutment, respectively. However, for the zirconia abutment, the odds were 0.87 and 7.5 times higher than the titanium group. CONCLUSIONS: The tissue around the gold alloy abutments resulted in worse attachment conditions compared with the titanium and zirconia abutments. Inflammation tended to be higher in the tissue around the gold alloy abutments than the titanium and zirconia abutments.

Intoxicación ocupacional por mercurio y la neurotoxicidad / Occupational intoxication by mercury and neurotoxicity

Introducción: El mercurio es un metal pesado que puede encontrarse en la naturaleza en 3 formas primarias: elemental, orgánico e inorgánico. Metodología: Se describe el caso de un varón de 30 años, profesión calderero, que formo parte de unos de los equipos encargados de sustituir los tubos de acero-carbono del intercambiador por donde circulan gases sulfurosos con restos de mercurio. Los síntomas iniciales fueron diarreas e inflamación de encías, presentando inicialmente una concentración de Hg en orina 939 mcg/L(VN≤30mcg/L), no recibiendo tratamiento hasta después de 6 meses con DMPS en dos oportunidades viendo una reducción de valores urinarios de 1830,47 a 7,38mcg/L. Como clínica, tuvo un eretismo mercurial severo, un trastorno visual complejo y un síndrome diarreico por neuropatía autonómica. Conclusión:Este trabajo pretende advertir sobre las consecuencias de la exposición prolongada a mercurio elemental, especialmente para el sistema nervioso central, así como el diagnóstico precoz y el tratamiento oportuno (AU)

Introduction: Mercury is a heavy metal that can be found in nature in 3 primary forms: elemental; organic and inorganic. Intoxication of occupational origin is widely identified as occupational disease. Methodology: The case of a 30-year-old man, a boilermaker (welder assembler), is described as one of the teams responsible for replacing the carbon steel tubes of the exchanger where sulfur gases with mercury traces circulate. The initial symptoms were diarrhea with mucus and blood and inflammation of the gums, initially presenting a blood Hg concentration of 475.9mcg / L (VN = <10mcg / L) and a concentration of Hg in urine 939mcg / L (VN = <30mcg / L), not receiving treatment until after 6 months with DMPS on two occasions seeing a reduction of urinary values from 1830.47 to 7.38mcg / L. As a clinical result, he had severe mercurial erythemia, a secondary visual complex disorder, and a secondary autonomic neuropathic diarrheal syndrome. Consequently, this fact at the beginning was declared as an occupational accident, however, due to its evolution the INSS, a year later, gave the declaration of professional illness caused by mercury, thus was also given the absolute permanent disability for any profession or trade. Conclusion: The present paper aims to warn about the consequences of prolonged exposure to elemental mercury especially for the central nervous system, as well as early diagnosis and timely treatment. On the other hand, note the importance of adopting an adequate and effective preventive system to protect the health of workers exposed to mercury (AU)

Effects of polyhexamethylene guanidine phosphate on human gingival fibroblasts.

OBJECTIVE: Polyhexamethylene guanidine phosphate (PHMG-P) was compared to chlorhexidine (CHX) in order to determine potential cytotoxic and immune-modulatory effects on human gingival fibroblasts. MATERIALS AND METHODS: Cytotoxic effects of PHMG-P and CHX on human gingival fibroblasts were assessed using cell viability assay at various time points and concentrations. The effects of PHMG-P and CHX on the secretion of prostaglandin (PG) E2, interleukin (IL)-6, IL-8 and matrix metalloproteinase (MMP)-1 by non-stimulated or IL-1ß stimulated fibroblasts were evaluated by enzyme-linked immunosorbent assays. RESULTS: PHMG-P concentration 0.00009% led to the total loss of fibroblast viability within 24 h, whereas inhibition of fibroblast viability by CHX occurred at significantly higher concentrations of 0.0009% (p < .001). Short-term exposure to 0.005% PHMG-P led to loss of fibroblast viability after 5 min, whilst cells exposed to 0.005% CHX survived 30 min of treatment (p < .001). IL-1ß stimulation induced an inflammatory response with a significant increase in the secretion of PGE2, IL-6, IL-8 and MMP-1. Treatment of IL-1ß stimulated fibroblasts in combination with PHMG-P or CHX at concentrations of 0.000045 or 0.0.00009% resulted in significantly decreased PGE2, IL-6, IL-8 and MMP-1 levels. PHMG-P or CHX alone did not affect the baseline secretion of PGE2, IL-6, IL-8 or MMP-1 by gingival fibroblasts. CONCLUSIONS: Cytotoxic effects on gingival fibroblasts were triggered by both PHMG-P and CHX at concentrations below those used in clinical practice. The tested antiseptics did not cause inflammation and reduced IL-1ß-induced secretion of inflammatory mediators and collagenase by gingival fibroblasts, which suggests anti-inflammatory properties.

Proinflammatory effects and mechanisms of calprotectin on human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Calprotectin (S100A8/A9) is a heterodimer of S100A8 and S100A9 and is associated with multiple inflammatory diseases, including Crohn's disease, rheumatoid arthritis and periodontitis. Levels of calprotectin are elevated in the gingival crevicular fluid of patients with periodontitis; however, the effects of calprotectin on human gingival fibroblasts (HGFs) remain unknown. This study investigated the proinflammatory activity of calprotectin on HGFs and the functional receptors and signaling pathways engaged by calprotectin. MATERIAL AND METHODS: HGFs were stimulated by equimolar concentrations of S100A8 and/or S100A9, and the expression levels of interleukin (IL)-6 and IL-8 were detected using real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assays. The calprotectin receptors were identified by pre-incubating HGFs with the toll-like receptor (TLR) 4 inhibitor or the antibody targeting the advanced glycation end product receptor (RAGE). The involvement of reactive oxygen species (ROS) and signaling pathways were also investigated by treating HGFs with ROS inhibitor or specific pathway inhibitors, respectively. RESULTS: S100A9 and S100A8/A9 significantly upregulated IL-6 and IL-8 expression, which was inhibited upon treatment with the TLR4 inhibitor TAK242. Pretreatment with RAGE-blocking antibodies did not affect cytokine expression. Additionally, S100A9 promoted the production of IL-6 and IL-8 from HGFs via different signaling pathways. IL-6 expression was upregulated via the NF-κB, c-Jun amino-terminal kinase (JNK) 1/2 and p38 mitogen-activated protein kinase (MAPK) pathways, and IL-8 expression was upregulated via NF-κB, p38, JNK1/2 and extracellular-regulated kinase 1/2 MAPK pathways. The release of both cytokines was dependent upon the production of ROS. CONCLUSION: Our findings suggest that calprotectin exerts proinflammatory effects on HGFs via the S100A9 subunit and TLR4-mediated NF-κB and MAPK signaling pathways.