The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1.

Despite knowledge of the effects of toxic shock syndrome (TSS) toxin 1 (TSST-1) on the adaptive immune system, little is known about stimulation of the innate immune system, particularly epithelial cells. This study investigated the interactions of TSS Staphylococcus aureus and TSST-1 with human vaginal epithelial cells (HVECs) and porcine mucosal surfaces. When cocultured with HVECs for 6 h, TSS S. aureus MN8 proliferated, formed aggregates on the HVEC surfaces, and produced exotoxins. Receptor binding studies showed that 35S-TSST-1 bound to 5 x 10(4) receptors per HVEC, with saturation at 15 min. Affymetrix Human GeneChip U133A microarray analysis determined S. aureus MNSM (100 bacteria/HVEC) caused at least twofold up- or down-regulation of 410 HVEC genes by 6 h; these data were also confirmed with S. aureus MN8. TSST-1 (100 microg/ml) caused up- or down-regulation of 2,386 HVEC genes by 6 h. In response to S. aureus, the HVEC genes most up-regulated compared to those in controls were those coding for chemokines or cytokines--MIP-3alpha, 478-fold; GRO-alpha, 26-fold; GRO-beta, 14-fold; and GRO-gamma, 30-fold--suggesting activation of innate immunity. TSST-1 also caused up-regulation of chemokine/cytokine genes. Chemokine/cytokine gene up-regulation was confirmed by enzyme-linked immunosorbent assays measuring the corresponding proteins induced by S. aureus and TSST-1. S. aureus MN8, when incubated with porcine vaginal tissue, increased the flux of 35S-TSST-1 across the mucosal surface. This was accompanied by influx of lymphocytes into the upper layers of the tissue. These data suggest innate immune system activation through epithelial cells, reflected in chemokine/cytokine production and influx of lymphocytes, may cause changes in vaginal mucosa permeability, facilitating TSST-1 penetration.

Effect of ethanol on lipid metabolism and epithelial permeability barrier of skin and oral mucosa in the rat.

BACKGROUND: Ethanol consumption induces changes in lipid metabolism. This might be reflected locally as an alteration in the epithelial lipid barrier. METHODS: Rats were fed with an isocaloric liquid diet with, or without, ethanol (6.7%) and were sacrificed at 60 or 120 days. Plasma and liver triglycerides, gamma-glutamyl-transferase (GGTP) levels, and permeability (Kp) of skin and buccal mucosa to tritiated water and the tobacco carcinogen, nitrosonornicotine, were determined. RESULTS: Significant elevation of GGTP at 120 days and triglycerides at both 60 and 120 days was observed for rats fed with ethanol diet. For this diet, Kp values to both penetrants increased significantly for skin in rats after 120 days compared to all other groups. CONCLUSION: The parallel between changes in lipid metabolism and permeability suggests that one effect of ingested alcohol is to alter the lipid-containing permeability barrier of stratified squamous epithelium.

Penetration of toxic shock syndrome toxin-1 across porcine vaginal mucosa ex vivo: permeability characteristics, toxin distribution, and tissue damage.

OBJECTIVE: The purpose of this study was to evaluate transvaginal penetration of toxic shock syndrome toxin-1 and its effects on permeability and tissue integrity in vitro with the use of excised porcine vaginal mucosa. STUDY DESIGN: Permeability to tritiated water (1 and 10 microg/mL applied toxin) and transmucosal flux of (35)S-methionine-labeled toxic shock syndrome toxin-1 (10 and 20 microg/mL) for up to 12 hours were assessed with the use of a continuous flow perfusion system. The location of labeled toxin that penetrated the mucosal tissue strata was determined. The integrity of toxin-treated, intact, scalpel-incised tissue was evaluated histopathologically. RESULTS: Toxic shock syndrome toxin-1 caused a non-dose-dependent increase in mucosal permeability and traversed the intact mucosa at a low rate without disrupting tissue integrity. In incised vaginal mucosa, toxic shock syndrome toxin-1 induced subepithelial separation and atrophy that were analogous to clinically relevant vaginal lesions that were reported in fatal cases of menstrual toxic shock syndrome. CONCLUSION: An in vitro model could be used to demonstrate that toxic shock syndrome toxin-1 permeates the vaginal mucosa and distributes throughout the tissue. Histologic evaluation of tissues that were exposed to toxic shock syndrome toxin-1 demonstrated lesions that were similar to those lesions that were reported in cases of menstrual toxic shock syndrome.