Staphylococcus aureus enterotoxin A- and B-specific IgE in chronic obstructive pulmonary disease.

Sensitization to Staphylococcus aureus enterotoxins A (SEA) and B (SEB) has been associated with asthma severity, exacerbations, and disease control. Our study aimed to investigate if there are differences in serum SEA-IgE and SEB-IgE levels between patients with chronic obstructive pulmonary disease (COPD), asthma, and controls, and to assess the association between SE sensitization and COPD clinical parameters and Th2 inflammation biomarkers in two well-defined COPD cohorts. Our findings suggest that COPD patients do not exhibit higher SEA and SEB sensitization compared to asthma patients and controls. However, in COPD patients, the presence of atopy and allergy is associated with positivity for SEA-IgE and SEB-IgE. Consequently, these allergens may aid in identifying atopic or allergic subgroups within the COPD population, but they are not directly associated with the diagnosis of COPD, elevated circulating blood eosinophils, or fractional exhaled nitric oxide (FENO) levels.

Quantum dot bead-based competitive immunochromatographic assay for enterotoxin aureus A detection in pasteurized milk.

Staphylococcal enterotoxin A (SEA) is an important biotoxin, produced by Staphylococcus aureus under appropriate conditions, and often contaminates milk and dairy products. Herein, an anti-SEA monoclonal antibody (anti-SEA mAb) was prepared by injecting the SEA protein in BALB/c mice, and a novel immunochromatographic assay (ICA) was developed for the rapid and sensitive determination of SEA in pasteurized milk by using highly luminescent quantum dot beads (QB) as signal amplification probe. Given the 1020-fold enhancement in the photoluminescence intensity of QB to the original quantum dot, the proposed QB-ICA exhibits high sensitivity for SEA determination in real milk samples with a limit of detection of 1.89 ng/mL, and shows good dynamic linearity for SEA quantitative detection from 2 to 150 ng/mL within 15 min of test time. The proposed QB-ICA also shows good selectivity to SEA detection with a negligible cross-reaction to common analogs, including staphylococcal enterotoxins B, C, D, and E. In addition, the accuracy and precision of QB-ICA were assessed by analyzing SEA-fortified milk samples. The average recoveries of intra- and interassays range from 85.5 to 128.1%, and the coefficients of variation range from 4.6 to 14.2%, indicating an acceptable accuracy for the quantitative detection of SEA in real milk samples. In summary, this work provides a powerful and rapid analysis tool for the sensitive monitoring of SEA contamination in pasteurized milk samples.

BCL11B Upregulates the Expression of RelA in T Cells Stimulated with Staphylococcal Enterotoxin A.

We explored the potential link between RelA and BCL11B transcription factors. To this end, Jurkat and Raji cells (Jurkat:Raji 10:1), as well as normal human peripheral blood T cells, were activated by staphylococcal enterotoxin A (SEA) and the expressions of both BCL11B and RelA mRNA and proteins were detected. BCL11B small interfering RNA was then transduced into Jurkat cells. Under the effect of SEA stimulation, the expression of BCL11B and RelA mRNA increased in two types of T cell lines over time, and the results were comparable with the levels of expression of BCL11B and RelA proteins. In the BCL11B-knockdown cells, the expression of RelA protein did not increase. These findings suggest that BCL11B regulates RelA expression in Jurkat cells and human peripheral blood T cells from healthy donors via the T-cell receptor signaling pathway.

Effect of (-)-Epigallocatechin Gallate to Staphylococcal Enterotoxin A on Toxin Activity.

Staphylococcal enterotoxin A (SEA) functions both as superantigens that stimulate non-specific T cell proliferation as well as potent gastrointestinal toxins. We previously reported that (-)-epigallocatechin gallate (EGCG) binds to SEA. Therefore, the ability of EGCG to inhibit SEA toxin activity was examined. As a result, EGCG significantly decreased SEA-induced expression and production of interferon gamma (IFN-γ). In addition, EGCG inhibited SEA-induced spleen cell proliferation. To investigate the role of the galloyl group in EGCG on SEA cytotoxicity in more detail, the effect of the binding of a hydroxyl group at position 3 of the galloyl group in EGCG to SEA on SEA cytotoxicity was examined using two methylated EGCG. SEA cytotoxicity was significantly controlled in both (-)-3''-Me-EGCG and (-)-4''-Me-EGCG. These results suggest that EGCG inhibits toxic activity via direct interaction with SEA or without any interaction with SEA. The binding affinity between SEA and EGCG under in vivo conditions was examined using a model solution. Although after treatment under acidic and alkaline conditions, the presence of protein and the digestive tract model solution, EGCG still interacted with SEA. Our studies are the first to demonstrate the effect of the binding of EGCG to SEA on toxin activity.

[Behavior of Staphylococcus aureus and Staphylococcal Enterotoxins A and Q in Scrambled Eggs].

Staphylococcal food poisoning (SFP) is caused by Staphylococcus aureus, and its typical symptom of vomiting is evoked by staphylococcal enterotoxins (SEs). SEs are classified as classical and new types. SEQ is a new-type enterotoxin predicted to have a high potential risk for SFP. To elucidate the correlation between the number of S. aureus cells and the production of SEs as well as classical and new-type enterotoxins in the food environment, the numbers of S. aureus strain cells carrying sea and seq genes and the production of SEA and SEQ protein were examined under 3 pHs values (pH 6.0, 7.0 and 8.0) and 2 NaCl concentrations (0.5 and 1.0%) conditions. The experiments were performed at 25℃, resembling the setting of scrambled eggs at room temperature after cooking. By 24 hr after incubation, the cell number in the scrambled egg was ≥107/10 g, reaching 109/10 g by 48 hr under all conditions. The productions of both SEA and SEQ were detected in the scrambled egg under all conditions by 48 h. SEQ was detected from 24 hr at all 3 pH values in the egg containing 1.0% NaCl, whereas in the egg containing 0.5% NaCl, it was detected from 24 hr at pH 6.0 and from 48 hr at other pHs. The SEQ production was consistently 100-1,000 times less than that of SEA. These results suggest that the new-type enterotoxin SEQ has the potential to evoke symptoms related to SFP following the consumption of egg products cooked under relative lower pH and water activity.

Maternal immune activation with staphylococcal enterotoxin A produces unique behavioral changes in C57BL/6 mouse offspring.

Stimulation of the immune system during pregnancy, known as maternal immune activation (MIA), can cause long-lasting neurobiological and behavioral changes in the offspring. This phenomenon has been implicated in the etiology of developmental psychiatric disorders, such as autism and schizophrenia. Much of this evidence is predicated on animal models using bacterial agents such as LPS and/or viral mimics such as Poly I:C, both of which act through toll-like receptors. However, fewer studies have examined the role of direct activation of maternal T-cells during pregnancy using microbial agents. Bacterial superantigens, such as Staphylococcal Enterotoxin A and B (SEA; SEB), are microbial proteins that activate CD4+ T-cells and cause prominent T-cell proliferation and cytokine production. We injected pregnant and non-pregnant adult female C57BL/6 mice with 200 µg/Kg of SEA, SEB, or 0.9% saline, and measured splenic T-cell-derived cytokine concentrations (viz., IL-2, IFN-γ, IL-6, and IL-4) 2 h later; animals injected with SEA were also measured for splenic concentrations of TNF-α and IL-17A. Half of the injected pregnant animals were brought to term, and their offspring were tested on a series of behavioral tasks starting at six weeks of age (postnatal day 42 [P42]). These tasks included social interaction, the elevated plus maze (EPM), an open field and object recognition (OR) task, prepulse inhibition (PPI) of sensorimotor gating, and the Morris water maze (MWM). Results showed that SEA and SEB induced significant concentrations of all measured cytokines, and in particular IFN-γ, although cytokine responses were greater following SEA exposure. In addition, pregnancy induced an inhibitory effect on cytokine production. Behavioral results showed distinct phenotypes among offspring from SEA- or SEB-injected mothers, very likely due to differences in the magnitude of cytokines generated in response to each toxin. Offspring from SEA-injected mothers displayed modest decreases in social behavior, but increased anxiety, locomotion, interest in a novel object, and short-term spatial memory, while offspring of SEB-injected mothers only exhibited increased anxiety and locomotion. There were no deficits in PPI, which was actually pronounced in SEA and SEB offspring. Overall, the novel use of SEA and SEB as prenatal immune challenges elicited distinct behavioral profiles in the offspring that both mirrors and diverges from previous models of maternal immune activation in important ways. We conclude that superantigen-induced T-cell-mediated maternal immune activation is a valid and valuable model for studying and expanding our understanding of the effects of prenatal immune challenge on neurodevelopmental and behavioral alterations in offspring.

Myositis in Lewis rats induced by the superantigen Staphylococcal enterotoxin A.

The aetiology of inflammatory myopathies is not clearly known. A predominance of activated Cd8+ T lymphocytes in inflammatory infiltrates has already been detected. Superantigens activate lymphocytes in an oligoclonal manner. In the present investigation, we investigated local effects after injection of the superantigen (Sag) Staphylococcus enterotoxin A (SEA) in the quadriceps femoris muscle of Lewis rats. Histopathology and gene expression profiling was performed after injection of SEA or saline (control group) after one, three and 10 days. Histology revealed focal myositis predominated by Cd8+ T lymphocytes with a perimysial, endomysial and perivascular distribution, peaking 3 days after SEA injection. Using DNA microarray analysis (Affymetrix Rat Genome 230 2.0) genes that were differentially over-expressed at least 15 times at days one, three or ten after SEA injection were further analysed. One day after SEA injection over-expressed genes were related to the immune response (e.g. Fcnb, CD8a) but also to cell proliferation, differentiation and migration (e.g. Mpp2). Three days after SEA injection, differentially overexpressed genes were mainly related to the immune reaction with a clear signature for a Cd8+ T lymphocyte response (e.g. Cd3d, Cd8, Prf1, Gzmb). Ten days after SEA injection, the differentially overexpressed genes were again associated with the immune reaction (e.g. Cd3d, Il2) but also with regenerative processes and wound healing (e.g. Tgfa, Tpm1, Ripply1). The inflammatory response induced by SEA in Lewis rats shares histological and molecular similarities to polymyositis in humans. Therefore, SEA induced myositis can be taken as a new and apt model for polymyositis.

Manufacturing of a novel double-function ssDNA aptamer for sensitive diagnosis and efficient neutralization of SEA.

Staphylococcal enterotoxin A (SEA) is an enterotoxin produced mainly by Staphylococcus aureus. In recent years, it has become the most prevalent compound for staphylococcal food poisoning (SFP) around the world. In this study, we isolate new dual-function single-stranded DNA (ssDNA) aptamers by using some new methods, such as the Taguchi method, by focusing on the detection and neutralization of SEA enterotoxin in food and clinical samples. For the asymmetric polymerase chain reaction (PCR) optimization of each round of systematic evolution of ligands by exponential enrichment (SELEX), we use Taguchi L9 orthogonal arrays, and the aptamer mobility shift assay (AMSA) is used for initial evaluation of the protein-DNA interactions on the last SELEX round. In our investigation the dissociation constant (KD) value and the limit of detection (LOD) of the candidate aptamer were found to be 8.5 ±â€¯0.91 of nM and 5 ng/ml using surface plasmon resonance (SPR). In the current study, the Taguchi and mobility shift assay methods were innovatively harnessed to improve the selection process and evaluate the protein-aptamer interactions. To the best of our knowledge, this is the first report on employing these two methods in aptamer technology especially against bacterial toxin.

Binding of Catechins to Staphylococcal Enterotoxin A.

Staphylococcal enterotoxin A (SEA) is a toxin protein, and is the most common cause of staphylococcal food poisoning. Polyphenols, such as catechins, are known to interact with proteins. In this study, we investigated the binding of catechins to SEA using SPR (Biacore), Fourier transform infrared spectroscopy (FT-IR), isothermal titration calorimetry (ITC), and protein-ligand docking. We found that (−)-epigallocatechin gallate (EGCG) could strongly bind to SEA. According to thermodynamic parameters, a negative ΔG indicated that the interaction between EGCG and SEA was spontaneous, and the electrostatic force accompanied by hydrophobic binding forces may play a major role in the binding. Data from Western blot analysis and docking simulation suggest that the hydroxyl group at position 3 of the galloyl group in the catechin structure was responsible for binding affinity with the Y91 of the A-6 region of SEA active sites. Our results provide further understanding of the binding interactions between catechins and SEA, and the inhibition of toxin activities by catechins.

PBMC activation via the ERK and STAT signaling pathways enhances the anti-tumor activity of Staphylococcal enterotoxin A.

Staphylococcal enterotoxin A (SEA) is well known as a superantigen and is highly potent in activating T lymphocytes. And it has been used clinically as an immunomodifier in the treatment of a number of tumors for years. However, the mechanism of its action remains largely unclear. In this study, SEA was found to significantly inhibit the proliferation and induce the death of human lung carcinoma A549 cells when co-cultured with human peripheral blood mononuclear cells (PBMCs). SEA could also induce the proliferation of human PBMCs and stimulate human PBMCs to release a wide range of cytokines that have broad anti-tumor activities such as IFN-γ, TNF-α, IL-2. Furthermore, SEA was found in PBMCs to induce a rapid and long-lasting phosphorylation of extracellular signal-regulated kinases (ERKs) which was significantly inhibited by MEK/ERK pathway inhibitors U0126 and PD0325901, and a late onset of phosphorylation of signal transducers and activators of transcription (STATs) which was significantly inhibited by a pan-JAK inhibitor Pyridone 6 (P6). Unexpectedly constitutive ERK or STATs phosphorylation was also significantly inhibited by P6 or U0126 in a dose-dependent manner, respectively. Summing up, our data reveal SEA may function as a novel protein drug used for cancer immunotherapy via inducing activation of PBMCs, immune cell crosstalk-dependent activation of ERK and STATs, and production of tumor-suppressive cytokines.

Gold nanoparticle-based localized surface plasmon immunosensor for staphylococcal enterotoxin A (SEA) detection.

We describe the engineering of stable gold nanoparticle (AuNP) bioconjugates for the detection of staphylococcal enterotoxin A (SEA) using localized surface plasmon resonance (LSPR). Two types of AuNP bioconjugates were prepared by covalently attaching anti-SEA antibody (Ab) or SEA to AuNPs. This was achieved by reacting Traut's reagent with lysine residues of both proteins to generate thiol groups that bind to gold atoms on the AuNP surface. These bioconjugates were characterized in-depth by absorption spectroscopy, cryo-transmission electron microscopy, dynamic light scattering, and zeta potential measurements. Their stability over time was assessed after 1 year storage in the refrigerator at 4 °C. Two formats of homogeneous binding assays were set up on the basis of monitoring of LSPR peak shifts resulting from the immunological reaction between the (i) immobilized antibody and free SEA, the direct assay, or (ii) immobilized SEA and free antibody, the competitive assay. In both formats, a correlation between the LSPR band shift and SEA concentration could be established. Though the competitive format did not meet the expected analytical performance, the direct format, the implementation of which was very simple, afforded a specific and sensitive response within a broad dynamic range-nanogram per milliliter to microgram per milliliter. The limit of detection (LOD) of SEA was estimated to equal 5 ng/mL, which was substantially lower than the LOD obtained using a quartz crystal microbalance. Moreover, the analytical performance of AuNP-Ab bioconjugate was preserved after 1 year of storage at 4 °C. Finally, the LSPR biosensor was successfully applied to the detection of SEA in milk samples. The homogeneous nanoplasmonic immunosensor described herein provides an attractive alternative for stable and reliable detection of SEA in the nanogram per milliliter range and offers a promising avenue for rapid, easy to implement, and sensitive biotoxin detection. Sensitive LSPR Biosensing of SEA in buffer and milk using stable AuNP-Antibody bioconjugates Graphical abstract.

Degradation of staphylococcal enterotoxin A by a Pseudomonas aeruginosa isolate from raw milk.

Recently, we found that staphylococcal enterotoxin A (SEA)-producing Staphylococcus aureus strains produced SEA in raw milk with microbial contaminants at high temperatures like 40 °C only. Moreover, the concentration of SEA produced in raw milk gradually decreased after the peak. The reason(s) for SEA degradation in raw milk was studied in this study. Degradation of SEA spiked in raw milk was observed at 40 °C, but not at 25 °C. A Pseudomonas aeruginosa isolate from raw milk degraded SEA spiked in broth at 40 °C. A sample partially purified with a chromatographic method from culture supernatant of the isolate degraded SEA. Two main proteolytic bands were observed in the sample by zymographic analysis with casein. These results suggested that the SEA in raw milk might be degraded by a protease(s) produced by the P. aeruginosa isolate. This finding might be the first report on SEA degradation by a proteolytic enzyme(s) derived from Pseudomonas bacteria to our knowledge.

Inhibitory effects of food additives derived from polyphenols on staphylococcal enterotoxin A production and biofilm formation by Staphylococcus aureus.

In this study, we examined the inhibitory effects of 14 food additives derived from polyphenol samples on staphylococcal enterotoxin A (SEA) production and biofilm formation by Staphylococcus aureus. Tannic acid AL (TA), Purephenon 50 W (PP) and Polyphenon 70A (POP) at 0.25 mg/mL and Gravinol®-N (GN), Blackcurrant polyphenol AC10 (BP), and Resveratrol-P5 (RT) at 1.0 mg/mL significantly decreased SEA production by S. aureus C-29 (p < 0.05). TA, GN, BP, and RT significantly inhibited the expression of the sea gene in S. aureus C-29 (p < 0.05), while suppression attempts by PP and POP proved unsuccessful. After result analysis, it can be derived that TA, GN, BP, and RT inhibit the production of SEA. Of the six samples, each one significantly inhibited biofilm formation (p < 0.05). Food additives derived from polyphenols have viability to be used as a means to inhibit the enterotoxin production and control the biofilm formation of foodborne pathogens.

Cyclization enhances function of linear anti-arthritic peptides.

This study describes the biophysical and immunomodulatory features of a cyclic peptide termed C1 which consists of alternating d-, l-amino acids and is capable of inhibiting IL-2 production in vitro and reducing the induction and extent of T-cell mediated inflammation in animal models. Solid-state nuclear magnetic resonance demonstrates that the peptide orders the lipid bilayer, suggesting a transmembrane orientation, and this is supported by surface plasmon resonance indicating strong binding affinity of C1 to model membranes. In vitro cell viability and proliferation assays show that C1 does not disrupt the integrity of cell surface membranes. Permeation studies of C1 and analogs across human epidermis cells show that the stability and skin permeability are enhanced by cyclization. Treatment with C1 in an asthma and in an arthritis animal model resulted in a suppressed immune response. Cyclization may be a useful means of enhancing biological linear peptide activity and improving delivery.

Expression and characterization of single-chain variable fragment antibody against staphylococcal enterotoxin A in Escherichia coli.

The staphylococcal enterotoxins (SEs) are potent gastrointestinal exotoxins synthesized by Staphylococcus aureus, which is responsible for various diseases including septicemia, food poisoning, and toxic shock syndrome, as well as bovine mastitis. Among them, staphylococcal enterotoxin A (SEA) is one of the most commonly present serotypes in staphylococcal food poisoning cases. In this study, the stable hybridoma 3C12 producing anti-SEA monoclonal antibody was established with an equilibrium dissociation constant (KD) of 1.48 × 10(-8) mol·L(-1), its ScFv-coding genes were obtained and then the anti-SEA single chain variable fragment (ScFv) protein was expressed in Escherichia coli. Characterization of the expressed target ScFv protein was analyzed by sodium dodecyl sulfate - polyacrylamide gel electrophoresis, Western blot, and enzyme-linked immunosorbent assay. The results demonstrated that the recombinant anti-SEA ScFv protein retained a specific binding activity for SEA, and the KD value of the soluble ScFv was about 3.75 × 10(-7) mol·L(-1). The overall yield of bioactive anti-SEA ScFv in E. coli flask culture was more than 10 mg·L(-1).

Integrating lateral flow device with controllable gold in situ growth for sensitive detection of staphylococcal enterotoxin A in milk.

Gold nanoparticle-based lateral flow immunoassays (AuNP-LFIA) are widely used for pathogen monitoring to prevent foodborne illness outbreaks. However, conventional AuNP-LFIA exhibits poor sensitivity and limited quantitative capacity due to the low colorimetric signal intensity of AuNPs. Herein, we introduced a low-background gold in situ growth (GISG) strategy by lowering the pH of the growth solution to weaken the reducibility of hydroxylamine, thereby enhancing the sensitivity of AuNP-LFIA. Additionally, we developed a universal and manufacturable lateral flow device to streamline the GISG process. We applied this device to detect staphylococcal enterotoxin A (SEA), an exotoxin produced by Staphylococcus aureus. Under optimal conditions, the proposed device demonstrated superior practicality and excellent sensitivity for SEA detection, achieving a detection limit of 0.061 ng/mL with the total detection time of 37 min, showing 311 times more sensitive than the unamplified AuNP-LFIA. Furthermore, SEA detection in milk samples showed a strong correlation (R2 = 0.8845) with results obtained from a conventional ELISA kit. Therefore, this promising LFIA device offers a novel strategy with high sensitivity and practicality for in-field detection of Staphylococcus aureus and can be easily adapted for screening other foodborne pathogens.

Double-Enhanced Photothermal Lateral Flow Biosensor Based on Dual Gold Nanoparticle Conjugates.

Bacterial toxins emerge as the primary triggers of foodborne illnesses, posing a significant threat to human health. To ensure food safety, it is imperative to implement point-of-care testing methods. Lateral flow biosensors (LFBs) based on gold nanoparticles (GNPs) have been commonly used for rapid detection, but their applicationis limited by low sensitivity. Based on the localized surface plasmon resonance and photothermal effect of dual gold nanoparticle conjugates (DGNPs), we developed a smartphone-integrated photothermal LFB (PLFB) with double-enhanced colorimetric and photothermal sensitivity. Through numerical simulations, we verified that DGNPs have significantly enhanced photothermal performance compared to single 15 nm GNPs (SGNPs), and applied DGNPs in PLFB for the detection of staphylococcus enterotoxin A (SEA). The colorimetric and photothermal limits of detection of DGNPs-based PLFB for SEA were 0.091 and 0.0038 ng mL-1, respectively. Compared with the colorimetric detection of the SGNPs-based LFB, the colorimetric detection sensitivity of the DGNPs-based PLFB was increased by 10.7 times, and the photothermal detection sensitivity was further improved by 255.3 times. Moreover, the PLFB exhibits robust reproducibility and exceptional specificity and is applicable for detecting SEA in milk samples. This smartphone-integrated PLFB based on DGNPs allows users to detect toxins simply, conveniently, and quickly and has huge application potential in the field of food safety.

Increased numbers and suppressive activity of regulatory CD25(+)CD4(+) T lymphocytes in the absence of CD4 engagement by MHC class II molecules.

Mechanisms of central and peripheral tolerance prevent autoimmunity. Regulatory T cells inhibit the activation of potentially auto-reactive T cells in peripheral lymphoid organs. In transgenic mice in which all MHC class II molecules are incapable of binding to CD4, class II MHC-restricted T cells preferentially differentiated into immunosuppressive, regulatory T cells. In these mutant MHC class II transgenic mice, a subset of CD4(+) T cells constitutively expressed moderately elevated levels of CD25 and potently inhibited interleukin-2 secretion by T cells from normal mice in a cell-to-cell, contact-dependent manner. Immunosuppressive activity depended on activation of the regulatory T cells. Thus, CD25(+)CD4(+) T cells from mutant MHC class II transgenic mice resembled phenotypically and functionally a major subset of natural regulatory T cells in normal mice, but were two to three-times more abundant. These results further clarify the mechanisms that govern the differentiation and maintenance of CD25(+)CD4(+) regulatory T cells, and present avenues for immunomodulation.

Staphylococcal enterotoxin A induces DNA damage in hepatocytes and liver tissues.

Staphylococcal enterotoxin A (SEA) is a foodborne bacterial toxin that can cause food poisoning, but little research has been done on the DNA damage caused by SEA. The aim of this research was to investigate the action of SEA in inducing DNA damage and oxidative stress response in hepatocytes and liver tissues. After treating HL-7702 and BRL-3A cells with different concentrations of SEA (0, 300, 600 ng/mL and 0, 400, 800 ng/mL), the production of phosphorylated H2AX (γH2AX) and p53 binding protein 1 (53BP1) aggregates was detected by confocal fluorescence microscopy, and the increases in ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), p53 protein expression were assessed by Western blot analysis, while increased reactive oxygen species (ROS) content was confirmed by flow cytometry and fluorescence probe. The genotoxicity of SEA to cells was attenuated after the addition of an oxidative inhibitor, demonstrating that SEA induced intracellular DNA damage through the oxidative pathway and a dose-dependent relationship was observed between the oxidation index and SEA. These experimental results deepen our understanding of SEA damage to cells at the genetic level, and provide a new orientation for the prevention and cure of food borne diseases caused by Staphylococcal enterotoxins (SEs).

Regulation of Staphylococcal Enterotoxin-Induced Inflammation in Spleen Cells from Diabetic Mice by Polyphenols.

Patients with diabetes are known to be more susceptible to infections following the establishment of Staphylococcus aureus in their nasal passages and on their skin. The present study evaluated the effects of staphylococcal enterotoxin A (SEA) on the immune responses of spleen cells derived from diabetic mice, and examined the effects of polyphenols, catechins, and nobiletin on inflammation-related gene expression associated with the immune response. (-)-Epigallocatechin gallate (EGCG), possessing hydroxyl groups, interacted with SEA, whereas nobiletin, possessing methyl groups, did not interact with SEA. The exposure of spleen cells derived from diabetic mice to SEA enhanced the expression of interferon gamma, suppressor of cytokine signaling 1, signal transducer and activator of transcription 3, interferon-induced transmembrane protein 3, Janus kinase 2, and interferon regulatory factor 3, suggesting that SEA sensitivity is variable in the development of diabetes. Both EGCG and nobiletin changed the expression of genes related to SEA-induced inflammation in spleen cells, suggesting that they inhibit inflammation through different mechanisms. These results may lead to a better understanding of the SEA-induced inflammatory response during diabetogenesis, and the establishment of methods to control these effects with polyphenols.