Impact of Tongue Pressure and Peak Expiratory Flow Rate on Nutritional Status of Older Residents of Nursing Homes in Japan: A Cross-Sectional Study.

OBJECTIVES: Swallowing function is critical for continuing oral feeding to prevent frailty in older adults. In this study, we investigated the impact of tongue pressure and pulmonary function on the nutritional status of older adults. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study was conducted in Kitakyushu, Japan from August 2017 to November 2018. Fifty-two residents aged >65 years of age from three nursing care insurance facilities in Kitakyushu City, Japan were recruited. MEASUREMENTS: Oral health status, swallowing function, nutritional status using a mini nutritional assessment short form (MNA-SF), cognitive function, activities of daily living, peak expiratory flow rate (PEFR) for pulmonary function, and tongue pressure were assessed. The associations between nutritional status and the above factors were analysed using a logistic regression model. RESULTS: Participants were divided into two groups: well-nourished group (MNA-SF ≤12) and undernutrition group (MNA-SF <12). Multivariate logistic regression analysis revealed that the correlations of PEFR [odds ratio (OR) = 0.23, 95% confidence interval (CI) = 0.23-0.89 p=0.033) and tongue pressure (OR = 0.88, 95% CI = 0.88-0.99, p=0.029) remained significant even after adjustment with possible confounders. CONCLUSION: Maximum tongue pressure and PEFR in older adults were significantly associated with their nutritional status. These findings suggest that maintaining oral and pulmonary function may be a preventive factor against a decrease in the nutritional status of older frail adults.

Prolongation of Oral Phase for Initial Swallow of Solid Food is Associated with Oral Diadochokinesis Deterioration in Nursing Home Residents in Japan: A Cross-Sectional Study.

Background: Prolongation of bolus forming complicates ingestion, in particular in older adults. Objectives: The purpose of this study is to examine which oral functions are associated with prolongation of the oral phase of forming a bolus until swallowing in older adults. Design: Cross-sectional study. Setting: three nursing homes in Kitakyushu, Japan from August 2017 to October 2018. Participants: 39 adults >60-years. Measurements: Number of functional teeth, chewing ability, swallowing ability, tongue and cheek pressure, saliva flow rate, oral diadochokinesis, global cognitive function, and body mass index, were examined. Time of oral phase until the first swallowing of solid food was measured as the outcome of the study using video, and audio recording of the swallowing sound by a throat microphone, with the cutoff point designated at 30 s. Based on the oral phase, participants were divided in two groups: normal and prolonged. Results: The 39 enrolled participants had a median age of 87 years, 17.3% were men, and 48.7% had prolonged oral phase. In the prolonged group, the swallowing ability, saliva flow rate, tongue and cheek pressure, and oral diadochokinesis were significantly lower than in the normal group. Binomial logistic regression analysis revealed that oral phase prolongation was associated with oral diadochokinesis (odds ratio 0.81, 95% confidence interval 0.67-0.98) after adjusting for potential covariates. Conclusion: Oral diadochokinesis deterioration is significantly associated with oral phase prolongation for initial swallowing of solid food in older adults.

Swallowing disorders and 1-year functional decline in community-dwelling older adults receiving home care.

The purpose of this study was to clarify the effect of swallowing disorders on functional decline in community-dwelling older adults receiving home care. This was a 1-year follow-up survey of 176 individuals ≥60 years living at home and receiving homecare services, without total dependence in basic daily living activities, in two mid-sized municipalities in Fukuoka, Japan. Functional decline was measured using the Barthel index (BI), and the primary outcome was total dependence in basic daily living activities (BI ≤ 20 points). Swallowing function was assessed using cervical auscultation, and the primary predictor was swallowing disorders. Logistic regression models were used to assess univariate and multivariate associations between baseline swallowing function and functional decline during follow-up. During follow-up 16 (9.1%), the participants became totally dependent in basic daily living activities. The participants with swallowing disorders had 6.41 times higher odds of total dependence in basic daily living activities compared to participants with normal swallowing function. After adjusting for potential confounders, swallowing disorders were significantly associated with higher odds of total dependence in basic daily living activities (odds ratio = 5.21, 95% confidence interval = 1.33-20.44). Regarding swallowing disorders, the corresponding population attributable fraction (%) of the incidence of total dependence in basic daily living activities was 50.4%. The current findings demonstrated that swallowing disorders were associated with greater risk of functional decline in basic daily living activities among older adults living at home and receiving home nursing care. Maintenance and improvement of swallowing function may prevent late-life functional decline.

Effects of oral care with tongue cleaning on coughing ability in geriatric care facilities: a randomised controlled trial.

Methods for preventing aspiration pneumonia are needed soon in order to reduce mortality from aspiration pneumonia and promote the health of the elderly. The aim of this randomised controlled trial was to examine whether oral care with tongue cleaning improves coughing ability in elderly individuals living in geriatric care facilities. Participants comprised of 114 residents of 11 group homes and private nursing homes in Aso City in Kumamoto Prefecture. Participants were randomly assigned to either (i) a group that underwent routine oral care with tongue cleaning (intervention group; n = 58) or (ii) a group that underwent routine oral care alone (control group; n = 56). Coughing ability was evaluated by measuring peak expiratory flow (PEF) before and after 4 weeks of intervention. Before the intervention, PEF did not differ significantly between the intervention group (1·65 ± 1·11 L s-1 ) and control group (1·59 ± 1·05 L s-1 ; P = 0·658). However, on termination of the intervention, PEF was significantly higher in the intervention group (2·54 ± 1·42 L s-1 ) than in the control group (1·90 ± 1·20 L s-1 ; P = 0·014). After the intervention, PEF had increased significantly in both groups; however, this increase was significantly greater in the intervention group (0·90 ± 0·95 L s-1 ) than in the control group (0·31 ± 0·99 L s-1 ; P < 0·001). Oral care with tongue cleaning led to increased PEF, suggesting improved coughing ability. Oral care incorporating tongue cleaning appears to be important for preventing aspiration pneumonia.

Swallowing Function and Nutritional Status in Japanese Elderly People Receiving Home-care Services: A 1-year Longitudinal Study.

OBJECTIVES: Malnutrition is a serious health concern for frail elderly people. Poor oral function leading to insufficient food intake can contribute to the development of malnutrition. In the present study, we explored the longitudinal association of malnutrition with oral function, including oral health status and swallowing function, in elderly people receiving home nursing care. DESIGN: Prospective observational cohort study with 1-year follow-up. SETTING: Two mid-sized cities in Fukuoka, Japan from November 2010 to March 2012. PARTICIPANTS: One hundred and ninety-seven individuals, aged ≥ 60 years, living at home and receiving home-care services because of physical disabilities, without malnutrition. MEASUREMENTS: Oral health status, swallowing function, taking modified-texture diets such as minced or pureed foods, nutritional status, cognitive function, and activities of daily living were assessed at baseline. The associations between malnutrition at 1-year follow-up and these related factors were analyzed using a logistic regression model. RESULTS: Swallowing disorders [risk ratio (RR): 5.21, 95% confidence interval (95% CI): 1.65-16.43] were associated with malnutrition. On the other hand, oral health status did not have a direct association with malnutrition. CONCLUSION: Swallowing disorders may be associated with the incidence of malnutrition in elderly people receiving home-care. The findings indicate that maintaining swallowing function may contribute to the prevention of malnutrition in frail elderly people.

Expression levels of adiponectin receptors and periodontitis.

BACKGROUND AND OBJECTIVE: We recently showed that adiponectin, an adipocyte-derived cytokine, may function as a negative regulator of the Toll-like receptor signaling pathway and of osteoclast formation in periodontal disease. In this study, we investigated whether the expression levels of adiponectin receptors (AdipoR1 and AdipoR2) are related to the presence of periodontitis. MATERIAL AND METHODS: We initially examined, using RT-PCR, the expression of the AdipoR1 and AdipoR2 genes at the mRNA level in several oral tissues of C57BL mice. Next, we investigated (using real-time PCR assays) whether inflammatory cytokines, such as tumor necrosis factor-alpha, could affect the expression levels of these genes in human gingival fibroblasts. Lastly, we compared the expression levels of these receptor proteins in gingival tissues between two healthy subjects and five patients with severe periodontal disease using western blotting analysis. RESULTS: The AdipoR1 and AdipoR2 receptors were ubiquitously expressed in the oral tissues of mice. We observed that treatment with tumor necrosis factor-alpha could significantly reduce the expression levels of both AdipoR1 and AdipoR2 genes in human gingival fibroblasts. Moreover, we found that the expression of both receptors was lower in periodontal tissues from patients with severe periodontitis than in patients with healthy periodontal tissues. CONCLUSION: These observations suggest that adiponectin may not function efficiently in sites of periodontal disease because of a decrease in the number of its receptors, and this probable dysfunction may play a role in worsening periodontitis in patients.

Oral health and mortality risk from pneumonia in the elderly.

Although poor oral health influences the occurrence of pulmonary infection in elderly people, it is unclear how the degree of oral health is linked to mortality from pulmonary infection. Therefore, we evaluated the relationship between oral health and four-year mortality from pneumonia in an elderly Japanese population. The study population consisted of 697 (277 males, 420 females) of the 1282 individuals who were 80 years old in 1997. Data on oral and systemic health were obtained by means of questionnaires, physical examinations, and laboratory blood tests. One hundred eight of the study persons died between 1998 and 2002. Of these, 22 deaths were due to pneumonia. The adjusted mortality due to pneumonia was 3.9 times higher in persons with 10 or more teeth with a probing depth exceeding 4 mm (periodontal pocket) than in those without periodontal pockets. Therefore, the increase in teeth with periodontal pockets in the elderly may be associated with increased mortality from pneumonia.

Number of teeth and serum lipid peroxide in 85-year-olds.

OBJECTIVES: To investigate influence of dental status on systemic oxidative stress, we evaluated the association between number of teeth and serum lipid peroxide, an oxidative stress index, in 85-years old residents of Japan. METHODS: In October 2003, 207 subjects 85-years old agreed to participate in the present follow-up study after five years from the 8020 Data Bank Survey of Fukuoka prefecture in 1998. Dental health condition including number of teeth was examined by dentists. Data from 204 subjects (88 male, 116 female) who completed nonfasting venous blood examination including lipid peroxide and blood chemistry were analyzed. The examination included a medical questionnaire regarding smoking history, physical activity, alcohol consumption, educational duration, and regular dental care, anthropometric and manometric measurements. RESULTS: Albumin, lipids, and lipid peroxide in serum all were within the normal range. Number of teeth correlated positively with height and white blood cell count, and correlated negatively with lipid peroxide. In a multiple regression analysis to adjust for confounding factors, tooth number retained this correlation with lipid peroxide. By analysis of variance with a Bonferroni-Dunn correction, edentulous subjects showed significantly higher lipid peroxide than those retaining 20 teeth or more. CONCLUSION: The negative association between number of teeth and lipid peroxide links more teeth remaining with less oxidative stress in an 85-year-old population; this may decrease risk of atherosclerotic complications.

Relationship between chewing ability and 4-year mortality in a cohort of 80-year-old Japanese people.

OBJECTIVE: Poor oral health has been reported to be a risk indicator of mortality, however, few data are available regarding the relationship between chewing ability and mortality. We examined the relationship between self-assessed chewing ability and mortality in elderly subjects. DESIGN: Prospective study. SUBJECTS AND METHODS: Participating in the study were 697 people (277 males, 420 females) from 1282 individuals (80 years old) residing in Fukuoka Prefecture, Japan. Data on oral and systemic health status through questionnaires, accompanied by physical and laboratory blood examinations were obtained. Chewing ability was assessed based on the number of types of food each subject reported as able to chew by questionnaire. RESULTS: A total of 108 subjects died between 1998 and 2002. Those with the lowest number of chewable foods were associated with higher risk of mortality than those with the ability to chew all of the 15 types of food surveyed [hazard ratio (HR) = 2.38, 95% confidence interval (95% CI) = 1.07-5.29], though other parameters including current smoking, low serum albumin, and poor physical health status were more significant. Further, reduced chewing ability of soft foods increased the risk (HR = 2.65, 95% CI = 1.20-5.87). CONCLUSION: Chewing ability was associated with mortality in a population of 80-year-old community residents, and may be a predictor for survival rate.

Local delivery system of cytotoxic agents to tumors by focused sonoporation.

Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. The cytotoxicity of bleomycin (BLM) was investigated using flow-cytometric analysis and Hoechst's staining in vitro assay systems. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. Histological analysis revealed that the cytotoxic effect was mainly apoptosis. We previously reported that the cytolethal distending toxin B (cdtB) from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporation-induced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo. These findings suggest that local administration of cytotoxic agents with sonoporation is a useful method for molecular cancer therapy.

Chewing ability and quality of life in an 80-year-old population.

As quality of life (QOL) could be influenced by oral status in the elderly, we examined whether chewing ability or number of teeth affected QOL in 80-year olds. A cross-sectional survey included dental examination, chewing self-assessment, and a QOL questionnaire. A total of 823 people who were 80 years old participated in this study. QOL was assessed in terms of satisfaction with physical condition, meals, daily living and social interactions, and with face-scale scores. After adjustment for gender, spouse and activities of daily living, dissatisfaction with social interactions was 3.9 times more prevalent in individuals able to chew four foods or fewer than in those chewing 15. Dissatisfaction with physical condition, meals and daily living, and poor face-scale scores, were 2.7, 2.4, 3.4, and 2.4 times more prevalent, respectively, in subjects chewing four foods or fewer. The number of teeth showed little effect. In conclusion, self-assessed chewing ability but not number of teeth was associated with QOL in 80-year-old subjects.

Relationship of number of remaining teeth to health-related quality of life in community-dwelling elderly.

OBJECTIVE: The aim of this study was to evaluate the relationship between number of remaining teeth and health-related quality of life in community-dwelling elderly. SUBJECTS: A total of 207 participants who were community-dwelling, 85 years of age. Data were from a population-based study of age-related general and oral health in Fukuoka Prefecture, Japan. MEASUREMENTS: The Japanese version of the Short Form 36 Health Survey (SF-36). RESULTS: The mental component score for the participants, from the SF-36, was higher than the Japanese national norm for those aged > or = 70 years. There were no significant differences in the mean of any scores on the SF-36 by having spouse, living with family, or education level. The mean of the SF-36 scores of physical functioning (PF) and of the physical component scores were significantly higher in the 85-year-old participants with > or = 20 teeth than in those with < or = 19 teeth (p < 0.05 and p < 0.01 respectively). In addition, a significant difference (p < 0.05) was observed between the mean of participants with > or = 20 teeth and those with < or = 19 teeth after adjustment for region where the participant lived, activities of daily living (ADL), and sex. The PF (p < 0.001), role-physical (p < 0.005), bodily pain (p < 0.001), vitality (p < 0.001), social functioning (p < 0.05), and physical component (p < 0.001) scores were significantly higher in participants with a good activities of daily living (ADL) assessment. However, ADL was not associated with the number of teeth. CONCLUSIONS: The findings of the present study indicated that 85-year-old participants with > or = 20 teeth had better subjective physical health than those with < or = 19 teeth.

Cloning and expression of a Porphyromonas gingivalis gene for protoporphyrinogen oxidase by complementation of a hemG mutant of Escherichia coli.

Porphyromonas gingivalis, a bacterium implicated in periodontal pathogenesis, has a growth requirement for iron protoporphyrin IX. By complementation with a P. gingivalis 381 chromosomal DNA library, we were able to isolate a clone that enhanced the poor growth of a hemG mutant of Escherichia coli. The DNA sequence analysis of this clone revealed three open reading frames (ORFs). ORF3 encoded a protein of 466 amino acids with a calculated molecular weight of 51 695 Da. The deduced amino acid sequence of the ORF3 gene had significant similarity to sequences of protoporphyrinogen oxidase (PPO) from Myxococcus xanthus (30% identical residues). When the ORF3 gene was overexpressed in E. coli, the extract had much higher PPO activity than a control extract, and this activity was inhibited by acifluorfen, a specific inhibitor of PPO. Thus, ORF3 was named PgHemG. Furthermore, several porphyrin-related genes, including hemD, hemN and hemH, were identified in the data bases on the websites available on-line. We postulated that a porphyrin biosynthetic pathway to heme from preuroporphyrin may be conserved in P. gingivalis.

Association of body mass index with blood pressure in 80-year-old subjects.

OBJECTIVE: Little data are available on the association between obesity and high blood pressure in elderly individuals, particularly in subjects over 80 years of age. The aim of the present study was to determine the association between body mass index (BMI) and blood pressure in 80-year-old subjects. METHODS: This study was part of the 8020 Data Bank Survey, which was designed to collect the baseline data of systemic and dental health conditions in 80-year-old subjects. We studied the cross-sectional association of BMI with blood pressures in 645 Japanese (258 men and 387 women), who were 80 years old. RESULTS: Mean systolic blood pressure rose from 146.6 mmHg in the first quintile of BMI to 147.5 mmHg in the second, 150.3 mmHg in the third, 151.6 mmHg in the fourth, and 156.4 mmHg in the fifth quintiles (test for trend, P = 0.006). Mean diastolic blood pressure rose from 75.8 mmHg in the lowest quintile of BMI to 81.8 mmHg in the highest (test for trend, P = 0.002). We performed multiple regression analysis, controlling for factors known to influence blood pressure values, such as sex, alcohol intake, current smoking status and serum glucose, total cholesterol and creatinine concentrations. The association between BMI and systolic and diastolic blood pressure, respectively, was highly statistically significant in all analyses. CONCLUSION: These results show that a close relationship is present between obesity and high blood pressure, even in very old subjects.

Relationship between tooth loss and electrocardiographic abnormalities in octogenarians.

Recent reports have suggested that periodontal disease is a risk factor for coronary heart disease (CHD). However, little is known about the relationship between periodontal disease and CHD in the very elderly. Therefore, we evaluated the association between tooth loss and abnormal ECG findings in octogenarians. Of the 1,282 octogenarians in Fukuoka Prefecture, Japan, 697 participated. Oral examinations--including a tooth count and an assessment of the Community Periodontal Index--and a 12-lead ECG were performed. Logistic regression analysis revealed that individuals with < 20 teeth had increased prevalence of ST segment depression, and T-wave abnormalities, after we adjusted for gender, smoking, serum cholesterol and glucose, blood pressure, and body mass index. Compared with individuals with > or = 20 teeth, edentulous individuals had an increased prevalence of T-wave abnormalities and arrhythmias after adjustment for coronary risk factors. We conclude that tooth loss may be an independent predictor of abnormal ECG findings in octogenarians.

Recombinant Actinobacillus actinomycetemcomitans cytolethal distending toxin proteins are required to interact to inhibit human cell cycle progression and to stimulate human leukocyte cytokine synthesis.

It has recently been discovered that Actinobacillus actinomycetemcomitans, an oral bacterium causing periodontitis, produces cytolethal distending toxin (CDT), a cell cycle-modulating toxin that has three protein subunits: CdtA, CdtB, and CdtC. In this study, we have cloned and expressed each toxin gene from A. actinomycetemcomitans in Escherichia coli and purified the recombinant Cdt proteins to homogeneity. Individual Cdt proteins failed to induce cell cycle arrest of the human epithelial cell line HEp-2. The only combinations of toxin proteins causing cell cycle arrest were the presence of all three Cdt proteins and the combination of CdtB and CdtC. A similar experimental protocol was used to determine if recombinant Cdt proteins were able to induce human peripheral blood mononuclear cells (PBMCs) to produce cytokines. The individual Cdt proteins were able to induce the synthesis by PBMCs of interleukin-1beta (IL-1beta), IL-6, and IL-8 but not of tumor necrosis factor alpha, IL-12, or granulocyte-macrophage colony-stimulating factor, with CdtC being the most potent and CdtB being the least potent cytokine inducer. There was evidence of synergism between these Cdt proteins in the stimulation of cytokine production, most markedly with gamma interferon, which required the minimum interaction of CdtB and -C to stimulate production.

Purification and characterization of alkaline phosphatase containing phosphotyrosyl phosphatase activity from the bacterium Prevotella intermedia.

A novel alkaline phosphatase, designated PiALP, has been purified and characterized from Prevotella intermedia ATCC 25611, an anaerobe implicated in progressive periodontal disease. The enzyme was a homodimer of apparently identical subunits of Mr 54 kDa. Thiol-reducing agents completely inhibited the purified enzyme. The enzyme was highly stable even at 80 degrees C. It exhibited substantial activity against tyrosine-phosphate-containing Raytide. The phosphatase activity was sensitive to orthovanadate and Zn2+ but highly resistant to okadaic acid. The amino acid sequence of peptides derived from PiALP showed a high degree of identity (65%) with alkaline phosphatases from Zymomonas mobilis and Synechococcus. The present results imply that PiALP might represent a new family of alkaline phosphotyrosyl phosphatases which has not been described previously.

Increase in Bcl-2 level promoted by CD40 ligation correlates with inhibition of B cell apoptosis induced by vacuolar type H(+)-ATPase inhibitor.

We have previously demonstrated that cell death of WEHI-231 cells induced by specific inhibitors of vacuolar type H(+)-ATPase (V-ATPase) occurs through apoptosis. CD40 is involved in regulating activation, differentiation, and apoptosis of B cells. Here we show that the CD40 ligation rescues WEHI-231 cells from apoptotic cell death induced by a specific V-ATPase inhibitor, concanamycin A. CD40 signaling with anti-CD40 antibody resulted in the induction of Bcl-2 and Bcl-XL proteins in WEHI-231 cells. Constitutive expression of Bcl-2 but not Bcl-XL inhibited concanamycin A-induced apoptosis. These findings suggest that the expression of Bcl-2 mediated through CD40 signaling rescues the apoptotic cell death induced by blockade of V-ATPase. Interestingly, the acidification of intracellular acidic compartments was completely inhibited when WEHI-231 cells were cultured with concanamycin A, even in the presence of anti-CD40 antibody. In addition, apoptosis in WEHI-231 cells induced by concanamycin A was strongly suppressed when cultured with imidazole, a cell-permeable base, suggesting that apoptosis induced by concanamycin A is preceded by intraacidification.

Role of CD14 molecules in internalization of Actinobacillus actinomycetemcomitans by macrophages and subsequent induction of apoptosis.

We report the evidence for apoptosis in J774.1 cells by the periodontopathic bacterium Actinobacillus actinomycetemcomitans, suggesting that the ability of A. actinomycetemcomitans to promote apoptosis might be important in the initiation and development of periodontitis. In this study, we examined the role of macrophage CD14, anchored by a glycerophosphatidylinositol tail, in the induction of apoptosis by A. actinomycetemcomitans infection by using the parent J774.1 cells and CD14-defective mutant (LR-9) cells. A small number of A. actinomycetemcomitans Y4 cells inside the LR-9 cells compared with the number in J774.1 cells was detected by confocal scanning microscopy. We found that LR-9 cells showed a weak cytotoxic effect after being infected with A. actinomycetemcomitans Y4. Apoptotic cell death of LR-9 cells infected with A. actinomycetemcomitans Y4, compared with that of the parent J774.1 cells was almost undetectable, as shown by the proportion of fragmented DNA in agarose gel electrophoresis and by the terminal deoxynucleotidyl transferase-mediated dUTP end-labeling method. Flow cytometric cell cycle analysis of J774.1 cells infected with A. actinomycetemcomitans Y4 revealed the increased percentage of apoptotic cells with hypodiploid DNA. However, LR-9 cells infected with A. actinomycetemcomitans Y4 showed no increase in population of apoptotic nuclei compared with the noninfected cells. These findings suggest that the CD14 molecules may contribute to the phagocytosis of A. actinomycetemcomitans by J774.1 cells and regulate, at least in part, apoptotic cell death of macrophages infected with A. actinomycetemcomitans.

Evidence for apoptosis of murine macrophages by Actinobacillus actinomycetemcomitans infection.

The gram-negative bacterium Actinobacillus actinomycetemcomitans is considered an important etiological agent in periodontal diseases. In this study, we show that A. actinomycetemcomitans strains are cytotoxic for the murine macrophage cell line J774.1. On the other hand, Porphyromonas gingivalis strains, other gram-negative oral species implicated in adult periodontitis, showed weak cytotoxic effects. For this to occur, A. actinomycetemcomitans had to gain entry into the macrophages, since cytotoxicity was prevented by cytochalasin D. We demonstrate that cell death induced by A. actinomycetemcomitans Y4 occurs through apoptosis, as shown by changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of DNA fragmentation indicative of apoptosis. We further sought to determine whether the cytotoxicity induced by A. actinomycetemcomitans Y4 could be modulated by the protein kinase inhibitors H7 and HA1004. Apoptotic cell death induced by A. actinomycetemcomitans Y4 was suppressed by H7 but was relatively unaffected by HA1004. These findings suggest that the signals of protein kinases may regulate apoptosis induced by A. actinomycetemcomitans Y4. The ability of A. actinomycetemcomitans to promote the apoptosis of macrophages may be important for the initiation of infection and the development of periodontal diseases.