Biomedical subjects

Jean-San Chia

Publications and source records attributed to Jean-San Chia.

16 recordsLinked to original sources

PubMed2006

Differential regulation of Streptococcus mutans gtfBCD genes in response to copper ions.

To persist in the oral cavity, bacteria must be able to tolerate environmental fluctuation, particularly in pH, nutrients, and essential elements. Glucosyltransferases B, C, and D of Streptococcus mutans synthesize glucans, and play essential roles in the sucrose-dependent adhesion of the organism to tooth surfaces. Transcriptions of gtfB, gtfC, and gtfD could be differentially regulated through independent promoters. To test the hypothesis that environmental factors frequently encountered in the dental plaque might serve as effector molecules involved in regulation, transcripts of individual gtfs were identified by reverse transcriptase-polymerase chain reaction assay and confirmed by Northern blot analysis using anti-sense RNA probes. When S. mutans was grown in different medium at low pH, differential regulation of the gtfs was observed. More specifically, the transcription and translational expression of gtfD but not gtfB and gtfC was specifically induced by copper ion (Cu(2+)). The up-regulation was independent of the Cu(2+)-transport operon copYAZ. These findings support the involvement of Cu(2+) as an effector molecule in the regulation of S. mutans gtfD. Nutrient change dominates influence of pH but not the effect of Cu(2+).

Blotting, Northern↗

PubMed2006

Bactericidal effects of diode laser on Streptococcus mutans after irradiation through different thickness of dentin.

BACKGROUND AND OBJECTIVES: A reliable method to eradicate the bacteria of residual carious dentin has not yet been developed. The aim of this study was to evaluate the antibacterial effect of a diode laser on Streptococcus mutans through different thickness (500, 1,000, and 2,000 microm) of human dentin. The thermal effect of laser irradiation was also investigated. STUDY DESIGN/MATERIALS AND METHODS: Dentin specimens were inoculated with 2 microl of S. mutans on one side and irradiated by a diode laser on the other side with a power output ranging from 0.5 to 7 W. The laser tip was swept with the whole irradiation area of 7 mm x 3 mm at a speed of about 10 mm/second with a total irradiation time of 30 seconds. Cooling with distilled water (30 ml/minute) was applied simultaneously during laser irradiation. After laser irradiation, the bacteria was removed from the dentin surfaces and cultured for 48 hours at 37 degrees C anaerobically to assess the colony forming units (CFU) per ml. The morphology of the lased bacteria and the temperature rise during laser irradiation were observed by scanning electron microscope (SEM) and measured by thermocouple, respectively. RESULTS: The results revealed that 7 W of laser power could kill 97.7% of CFU through 500 microm thickness of dentin. However, the bactericidal efficiency was significantly reduced as the dentin thickness was increased. The morphological changes of lased bacteria ranged from less affected such as loss of their wall bands and existence of minicells to more severely degenerated, such as disintegration and fusion of cells with pores on the cell wall. Only the dentin specimens with a thickness of 500 microm exhibited a temperature rise greater than 5.5 degrees C after receiving 5 or 7 W of laser irradiation. CONCLUSIONS: A diode laser can eliminate the Streptococcus mutans of the residual carious dentin without inducing high pulpal temperature rise when the remaining dentin thickness is greater than 1 mm.

Dental Caries↗

PubMed2006

Levamisole can modulate the serum tumor necrosis factor-alpha level in patients with recurrent aphthous ulcerations.

BACKGROUND: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Tumor necrosis factor (TNF)-alpha is an important inflammatory mediator and a critical cytokine for adequate host defense. Our previous studies have shown that 14-43% and 59-63% of patients in the ulcerative stage of major, minor or herpetiform RAU have significantly higher than normal serum levels of interleukin (IL)-6 and IL-8, respectively. In this study, we examined whether RAU patients in the ulcerative stage had a significantly higher than normal serum level of TNF-alpha and assessed whether treatment with levamisole can modulate serum TNF-alpha levels in RAU patients. METHODS: This study used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of TNF-alpha in 146 patients with RAU, nine patients with traumatic ulcers (TU), and 54 normal control subjects. Fifty-five RAU patients with serum TNF-alpha levels higher than 5.0 pg/ml were treated with levamisole for 0.5-4 months and their serum TNF-alpha levels were measured after treatment. RESULTS: We found that 29% (42 of 146) RAU patients as well as 39% (24 of 61) major type, 20% (14 of 69) minor type, and 25% (four of 16) herpetiform type RAU patients had a serum level of TNF-alpha greater than the upper normal limit of 7.4 pg/ml. The mean serum level of TNF-alpha in patients with RAU (9.1 +/- 1.0 pg/ml, P < 0.001), major type RAU (11.6 +/- 1.9 pg/ml, P < 0.001), minor type RAU (6.9 +/- 0.9 pg/ml, P < 0.005), or herpetiform type RAU (9.6 +/- 2.7 pg/ml, P < 0.001) was higher than that (3.8 +/- 0.2 pg/ml) in normal control subjects. The mean serum TNF-alpha level was significantly higher in patients with major type RAU than in patients with minor type RAU (P < 0.05) and was significantly higher in major type RAU patients in the exacerbation stage than in the post-exacerbation stage (P < 0.05). In 55 RAU patients with serum TNF-alpha levels higher than 5.0 pg/ml, treatment with levamisole for a period of 0.5-4 months could significantly reduce the serum TNF-alpha level from 16.4 +/- 1.9 to 5.8 +/- 0.6 pg/ml (P < 0.001). CONCLUSIONS: We conclude that a significantly higher than normal serum level of TNF-alpha can be detected in 20-39% of patients in the ulcerative stage of major, minor or herpetiform RAU. The serum TNF-alpha level may be associated with the severity and the stage of RAU. Levamisole can modulate serum TNF-alpha levels in RAU patients.

Adjuvants, Immunologic↗

PubMed2006

Glucosyltransferases of viridans group streptococci modulate interleukin-6 and adhesion molecule expression in endothelial cells and augment monocytic cell adherence.

Recruitment of monocytes plays important roles during vegetation formation and endocardial inflammation in the pathogenesis of infective endocarditis (IE). Bacterial antigens or modulins can activate endothelial cells through the expression of cytokines or adhesion molecules and modulate the recruitment of leukocytes. We hypothesized that glucosyltransferases (GTFs), modulins of viridans group streptococci, may act directly to up-regulate the expression of adhesion molecules and also interleukin-6 (IL-6) to augment monocyte attachment to endothelial cells. Using primary cultured human umbilical vein endothelial cells (HUVECs) as an in vitro model, we demonstrated that GTFs (in the cell-bound or free form) could specifically modulate the expression of IL-6, and also adhesion molecules, in a dose- and time-dependent manner. Results of inhibition assays suggested that enhanced expression of adhesion molecules was dependent on the activation of nuclear factor kappaB (NF-kappaB) and extracellular signal-regulated kinase and that p38 mitogen-activated protein kinase pathways also contributed to the release of IL-6. Streptococcus-infected HUVECs or treatment with purified IL-6 plus soluble IL-6 receptor alpha enhanced the expression of ICAM-1 and the adherence of the monocytic cell line U937. These results suggest that streptococcal GTFs might play an important role in recruiting monocytic cells during inflammation in IE through induction of adhesion molecules and IL-6, a cytokine involved in transition from neutrophil to monocyte recruitment.

Cell Adhesion↗

PubMed2005

The chinese herbal medicine Tien-Hsien liquid inhibits cell growth and induces apoptosis in a wide variety of human cancer cells.

OBJECTIVE: Tien-Hsien liquid (THL) is a commercially available Chinese herbal mixture that has been used as an anticancer dietary supplement for more than 10 years. We recently showed that THL has strong immunomodulatory effects on peripheral blood mononuclear cells (PBMC) and T cells. To investigate the antitumor activity of THL further, we sought to test whether THL could induce apoptosis in various human cancer cell lines based on the fact that THL contains several components with tumor killing functions. DESIGN: The growth inhibitory effect of THL on human cervical carcinoma C-33A cells, human lung carcinoma H1299 cells, and human PBMC was assessed by counting viable cells using the trypan blue dye exclusion method. The apoptosis-inducing activity of THL in H1299 cells was assessed by analyzing the cells with four assays: (1) Hoechst 33258 nuclear DNA staining; (2) the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay; (3) the nucleosomal DNA fragment ladder assay; and (4) the sub-G1 cell analysis. The activities of caspase-8, -9, and -3 in H1299 cells treated with or without THL were also measured to elucidate the possible mechanism underlying THL apoptosis-inducing effect. Finally, the apoptotic effect of THL on fifteen human cancer cell lines and normal human cells were analyzed by the TUNEL assay. RESULTS: THL could induce apoptosis in all human cancer cell lines tested but not in normal human cells. THL treatment of H1299 cancer cells resulted in activation of caspase-8, -9, and -3 and the inhibitors of these caspases could partially block THL-induced apoptosis. CONCLUSIONS: THL has been used by numerous patients with cancer for many years with no known adverse effect. Our present study showing that THL had a broad-range tumor killing function has provided a molecular basis underlying THL therapeutic activity. Furthermore, because THL had apoptotic effects only on cancer cells but not on normal cells, this selectivity suggests that THL could be a potential cancer therapeutic agent.

Antineoplastic Agents↗

PubMed2005

Species identification of mutans streptococci by groESL gene sequence.

The near full-length sequences of the groESL genes were determined and analysed among eight reference strains (serotypes a to h) representing five species of mutans group streptococci. The groES sequences from these reference strains revealed that there are two lengths (285 and 288 bp) in the five species. The intergenic spacer between groES and groEL appears to be a unique marker for species, with a variable size (ranging from 111 to 310 bp) and sequence. Phylogenetic analysis of groES and groEL separated the eight serotypes into two major clusters. Strains of serotypes b, c, e and f were highly related and had groES gene sequences of the same length, 288 bp, while strains of serotypes a, d, g and h were also closely related and their groES gene sequence lengths were 285 bp. The groESL sequences in clinical isolates of three serotypes of S. mutans were analysed for intraspecies polymorphism. The results showed that the groESL sequences could provide information for differentiation among species, but were unable to distinguish serotypes of the same species. Based on the determined sequences, a PCR assay was developed that could differentiate members of the mutans streptococci by amplicon size and provide an alternative way for distinguishing mutans streptococci from other viridans streptococci.

Bacterial Proteins↗

PubMed2005

Glucosyltransferases of viridans streptococci are modulins of interleukin-6 induction in infective endocarditis.

The glucosyltransferases (GTFs) of viridans streptococci, common pathogens of infective endocarditis, are extracellular proteins that convert sucrose into exopolysaccharides and glucans. GTFs B, C, and D of Streptococcus mutans are modulins that induce, in vitro and in vivo, the production of cytokines, in particular interleukin-6 (IL-6), from monocytes. The roles of S. mutans GTFs in infectivity and inflammation in situ were tested in a rat experimental model of endocarditis. No significant differences in infectivity, in terms of 95% infective dose and densities of bacteria inside vegetations, were observed between laboratory strain GS-5 and two clinical isolates or isogenic mutant NHS1DD, defective in the expression of GTFs. In aortic valves and surrounding tissues, IL-6 was detected by Western blots and immunostaining 24 h after GS-5 infection, was maintained over 72 h, and was followed by production of tumor necrosis factor alpha but not IL-1beta. Animals infected with NHS1DD showed markedly lower levels of IL-6 (less than 5% of that of parental GS-5-infected rats), while tumor necrosis factor alpha was unaffected. In contrast, animals infected with NHR1DD, another isogenic mutant expressing only GtfB, showed a much smaller reduction (down to 56%). These results suggest that GTFs are specific modulins that act during acute inflammation, inducing IL-6 from endothelial cells surrounding the infected valves without affecting bacterial colonization in vegetations, and that IL-6 might persist in chronic inflammation in endocarditis.

Animals↗

PubMed2005

"Tien-Hsien liquid" can modulate antigen-stimulated cytokine production by T-cells isolated from patients with recurrent aphthous ulcerations.

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. Our previous study found that THL can modulate the antigen-stimulated proliferative response of peripheral blood mononuclear cells and T-cells isolated from RAU patients. In this study, we further tested whether THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. To achieve this goal, T-cells isolated from 19 RAU patients were incubated with phytohemagglutinin (PHA), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. The levels of interleukin (IL)-2, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IL-6, or IL-10 in the supernatants of T-cell cultures were measured by cytokine enzyme-linked immunosorbent assay (ELISA) kits. We found that THL significantly increased the PHA- or TT-stimulated TNF-alpha, IL-6, and IL-10 production by T-cells isolated from RAU patients. However, THL could also significantly decrease the TT-stimulated IL-2 production, the GtfD-stimulated IL-2, TNF-alpha, IL-6 and IL-10 production, and the S. mutans-stimulated IFN-gamma, TNF-alpha, and IL-10 production by T-cells isolated from RAU patients. These results indicate that THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. Because RAU is probably a Thl-mediated disease with elevated levels of IL-2, IFN-gamma, TNF-alpha and IL-6 in either the patient's sera or oral lesions and these increased levels of cytokines can be reduced by THL, we suggest that THL may be a potential immunoceutical agent for treatment of RAU.

Adult↗

PubMed2004

Platelet aggregation induced by serotype polysaccharides from Streptococcus mutans.

Platelet aggregation plays an important role in the pathogenesis of infective endocarditis induced by viridans streptococci or staphylococci. Aggregation induced in vitro involves direct binding of bacteria to platelets through multiple surface components. Using platelet aggregometry, we demonstrated in this study that two Streptococcus mutans laboratory strains, GS-5 and Xc, and two clinical isolates could aggregate platelets in an irreversible manner in rabbit platelet-rich plasma preparations. The aggregation was partially inhibited by prostaglandin I(2) (PGI(2)) in a dose-dependent manner. Whole bacteria and heated bacterial cell wall extracts were able to induce aggregation. Cell wall polysaccharides extracted from the wild-type Xc strain, containing serotype-specific polysaccharides which are composed of rhamnose-glucose polymers (RGPs), could induce platelet aggregation in the presence of plasma. Aggregation induced by the serotype-specific RGP-deficient mutant Xc24R was reduced by 50% compared to the wild-type strain Xc. In addition, cell wall polysaccharides extracted from Xc24R failed to induce platelet aggregation. The Xc strain, but not the Xc24R mutant, could induce platelet aggregation when preincubated with plasma. Both Xc and Xc24R failed to induce platelets to aggregate in plasma depleted of immunoglobulin G (IgG), but aggregation was restored by replenishment of anti-serotype c IgG. Analysis by flow cytometry showed that S. mutans RGPs could bind directly to rabbit and human platelets. Furthermore, cell wall polysaccharides extracted from the Xc, but not the Xc24R, strain could induce pseudopod formation of both rabbit and human platelets in the absence of plasma. Distinct from the aggregation of rabbit platelets, bacterium-triggered aggregation of human platelets required a prolonged lag phase and could be blocked completely by PGI(2). RGPs also trigger aggregation of human platelets in a donor-dependent manner, either as a transient and reversible or a complete and irreversible response. These results indicated that serotype-specific RGPs, a soluble product of S. mutans, could directly bind to and activate platelets from both rabbit and human. In the presence of plasma containing IgG specific to RGPs, RGPs could trigger aggregation of both human and rabbit platelets, but the degree of aggregation in human platelets depends on the donors.

Animals↗

PubMed2004

Immunomodulating effects of "tien-hsien liquid" on peripheral blood mononuclear cells and T-lymphocytes from patients with recurrent aphthous ulcerations.

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. In our institution, an immunomodulating agent, levamisole, is used to treat RAU with satisfactory therapeutic effect. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. To test whether THL has immunomodulating effects on antigen-stimulated proliferation response (PR) of peripheral blood mononuclear cells (PBMC) and T-cells isolated from RAU patients and to test whether THL is a potential drug for treating RAU, PBMC or T-cells isolated from RAU patients were incubated with lipopolysaccharides (LPS) from Escherica coli, phytohemagglutinin (PHA), staphylococcal enterotoxin B (SEB), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. We found that THL significantly increased the LPS-stimulated PR of PBMC from active RAU patients, the GtfD-stimulated PR of PBMC and of T-cells from inactive RAU patients, and the S. mutans-stimulated PR of PBMC from inactive RAU patients. However, THL could also significantly reduce the SEB-stimulated PR of PBMC and of T-cells from active RAU patients and S. mutans-stimulated PR of T-cells from active RAU patients. These results suggest that THL can modulate the antigen-stimulated PR of PBMC and T-cells from RAU patients. Therefore, it may be a potential immunoceutical agent for treatment of RAU.

Cell Culture Techniques↗

PubMed2004

Serum interleukin-8 level is a more sensitive marker than serum interleukin-6 level in monitoring the disease activity of recurrent aphthous ulcerations.

BACKGROUND: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Interleukin (IL)-8 is a pro-inflammatory cytokine of host response to injury and inflammation. Our recent study has found that measurement of serum IL-6 level can detect only 24% RAU patients with an abnormal serum level. In this study, we examined both the serum IL-6 and IL-8 levels in a group of RAU patients. The abilities of IL-6 and IL-8 to detect patients with an abnormal serum level were compared in order to find out whether IL-8 was a more sensitive serum marker than IL-6 in monitoring the disease activity of RAU. METHODS: In this study, we used a solid-phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 and IL-8 in 146 patients with RAU, 9 patients with traumatic ulcers (TU), and 54 normal control (NC) subjects. Eighty-two RAU patients, with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration, were treated with levamisole for 0.5-3.5 months, and their serum IL-6 and IL-8 levels were measured after treatment. RESULTS: We found that 25% (37/146) RAU patients, as well as 33% (20/61) major-type, 19% (13/69) minor-type, and 25% (4/16) herpetiform-type RAU patients, had a serum level of IL-6 greater than the upper normal limit of 4.7 pg/ml. In contrast, 60% (87/146) RAU patients, as well as 59% (36/61) major-type, 59% (41/69) minor-type, and 63% (10/16) herpetiform-type RAU patients, had a serum level of IL-8 greater than the upper normal limit of 8.7 pg/ml. In 82 RAU patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration, treatment with levamisole for a period of 0.5-3.5 months could significantly reduce the serum IL-6 level from 12.0 +/- 1.6 to 3.0 +/- 0.5 pg/ml (P < 0.001), and could significantly lower the serum IL-8 level from 70.9 +/- 11.2 to 13.8 +/- 3.1 pg/ml (P < 0.001). CONCLUSIONS: Because measurement of serum IL-8 level can detect 60% RAU patients with an abnormal serum level, while measurement of serum IL-6 level can detect only 25% RAU patients with an abnormal serum level, we conclude that serum IL-8 level is a more sensitive marker than serum IL-6 level in monitoring the disease activity of RAU. Levamisole can modulate both the serum IL-6 and IL-8 levels in RAU patients. IL-8, like IL-6, is also a useful serum marker in evaluating therapeutic effects of levamisole on RAU patients.

Adolescent↗

PubMed2003

Structural analysis of the functional influence of the surface peptide Gtf-P1 on Streptococcus mutans glucosyltransferase C activity.

Glucosyltransferases (GtfB/C/D) in Streptococcus mutans are responsible for synthesizing water-insoluble and water-soluble glucans from sucrose and play very crucial roles in the formation of dental plaque. A monoclonal antibody against a 19-mer peptide fragment named Gtf-P1 was found in GtfC to reduce the enzyme activity to 50%. However, a similar experiment suggested almost unchanged activity in GtfD, despite of the very high sequence homology between the two enzymes. No further details are yet available to elucidate the biochemical mechanism responsible for such discrimination. For a better understanding of the catalytic behavior of these glucosyltransferases, structural and functional analyses were performed. First, the exact epitope was identified to specify the residue(s) required for monoclonal antibody recognition. The results suggest that the discrimination is determined solely by single residue substitution. Second, based on a combined sequence and secondary structure alignment against known crystal structure of segments from closely related proteins, a three-dimensional homology model for GtfC was built. Structural analysis for the region communicating between Gtf-P1 and the catalytic triad revealed the possibility for an "en bloc" movement of hydrophobic residues, which may transduce the functional influence on enzyme activity from the surface of molecule into the proximity of the active site. Figure Side chain interactions between Gtf-P1 and catalytic Asp-477 in GtfC. Calpha-tracing of GtfC with the two crucial peptides (Gtf-P1, orange; Gtf-P2, blue) and the catalytic triad residues ( red) highlighted to show their relative spatial organization. Side chains for the residues are also depicted according to their atom types. The structure is viewed with the barrel opening facing down

Amino Acid Sequence↗

PubMed2003

Levamisole and Chinese medicinal herbs can modulate the serum interleukin-6 level in patients with recurrent aphthous ulcerations.

BACKGROUND: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that the high serum IL-6 levels in some RAU patients can be reduced by drug treatment. This finding suggests that IL-6 may be a useful marker in evaluating therapeutic effects of RAU. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 228 patients with RAU, erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some RAU patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5 months and their serum IL-6 levels were measured after treatment. RESULTS: We found that about 99% of the normal control subjects and the patients with EM, TU, or OSF had a serum IL-6 level within the normal limit of 5.0 pg/ml. However, 24% (48/197) RAU patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum level of IL-6 greater than 5.0 pg/ml. The mean serum level of IL-6 in patients with RAU (3.6 +/- 3.5 pg/ml, P < 0.001), minor type RAU (2.7 +/- 2.0 pg/ml, P < 0.05), major type RAU (5.2 +/- 4.6 pg/ml, P < 0.001), or herpetiform type RAU (4.1 +/- 3.8 pg/ml, P < 0.01) was higher than that in normal control subjects. The mean serum level of IL-6 in major type (P < 0.001) or in herpetiform type RAU patients (P < 0.05) was higher than that in minor type RAU patients. The mean reduction of serum IL-6 level (10.0 +/- 7.1 pg/ml) in RAU patients after treatment with levamisole plus Chinese medicinal herbs was significantly higher than that (5.1 +/- 3.7 pg/ml) in RAU patients after treatment with levamisole only (P < 0.005), suggesting that the combination therapy is superior to the single therapy of levamisole only. CONCLUSION: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in RAU patients. Although the therapeutic effect of RAU can be assessed by a decrease in the frequency, duration and number of the oral ulcerations, it can also be monitored by a reduction of serum IL-6 level in RAU patients.

Adjuvants, Immunologic↗

PubMed2002

Serum interleukin-6 level is a useful marker in evaluating therapeutic effects of levamisole and Chinese medicinal herbs on patients with oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5.5 months and their serum IL-6 levels were measured after treatment. RESULTS: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 +/- 3.1 pg/ml, P < 0.001), EOLP (3.4 +/- 3.2 pg/ml, P < 0.001), major type EOLP (4.9 +/- 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 +/- 3.0 pg/ml, P < 0.01), or NEOLP (4.2 +/- 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 +/- 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 +/- 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 +/- 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only. CONCLUSION: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.

Adjuvants, Immunologic↗

PubMed2002

Induction of cytokines by glucosyltransferases of streptococcus mutans.

Production of proinflammatory cytokines is implicated in the pathogenesis of viridans streptococcus-induced alpha-streptococcal shock syndrome and infective endocarditis. Streptococcus mutans, one of the opportunistic pathogens causing infective endocarditis, was reported previously to stimulate monocytes and epithelial and endothelial cells in vitro to produce various cytokines. We found that glucosyltransferases (GTFs) GtfC and GtfD of S. mutans stimulated predominantly the production of interleukin-6 (IL-6) from T cells cultured in vitro. The level of IL-6 but not of tumor necrosis factor alpha in blood was significantly elevated when rats were injected intravenously with S. mutans GS-5, whereas IL-6 was detected at a much lower level when rats were challenged with NHS1DD, an isogenic mutant defective in the expression of GTFs. The serum IL-6 level was elevated in patients with endocarditis caused by different species of viridans streptococci which express GTF homologues. Affinity column-purified GTFs reduced the levels of detectable IL-2 of T cells stimulated by another bacterial antigen, tetanus toxoid. These results suggested that GTFs might modulate the production of Th1-type cytokines and that GTFs of S. mutans play a significant role in stimulating the production of the proinflammatory cytokine IL-6 in vivo.

Adult↗

PubMed2002

Increased proliferative response of peripheral blood mononuclear cells and T cells to Streptococcus mutans and glucosyltransferase D antigens in the exacerbation stage of recurrent aphthous ulcerations.

BACKGROUND AND PURPOSE: Cytotoxic T lymphocyte-induced lysis of virus-infected oral epithelial cells has been shown to be a cause of early ulcer formation in recurrent aphthous ulcerations (RAU). To test whether bacteria and their associated antigens are involved in the disease process of RAU, the proliferative response (PR) to different streptococcal species in peripheral blood mononuclear cells (PBMC) and T cells isolated from RAU patients at the exacerbation stage was determined. METHODS: PBMC and T cells were isolated from 39 patients with RAU, 21 patients with erosive oral lichen plaus (EOLP, disease control group), and 22 healthy subjects (normal control group). Streptococcus mutans, Streptococcus sanguis, Streptococcus oralis, Streptococcus gordonii, Streptococcus mitis and their associated antigen, glucosyltransferase D (GtfD), were used to stimulate isolated PBMC and T cells in in vitro proliferation assays. RESULTS: PBMC and T cells isolated from RAU patients at the exacerbation stage showed a significantly higher PR to S. mutans antigen and GtfD than those isolated from EOLP patients or healthy control subjects (p < 0.05). GtfD was a more potent stimulation antigen than S. mutans. However, elevated PRs to S. mutans antigen and GtfD were transient and present only in the exacerbation stage of RAU. These elevated PRs declined to normal levels in the postexacerbation and convalescence stages of RAU. Furthermore, the GtfD-stimulated PR in PBMC and T cells was correlated with the severity of RAU. CONCLUSION: In addition to viral infections, streptococci and their associated antigen, GtfD, may be involved in the disease process of RAU, especially in the exacerbation stage.

Adolescent↗