Regulation of E-cadherin expression by dexamethasone and tumour necrosis factor-alpha in nasal epithelium.

Asthma and rhinitis often coexist and share many clinical features. The extent of epithelial alteration in nasal inflammation is controversial. Cell-cell adhesion plays an important role in tissue morphogenesis and homeostasis and is mediated by the cadherin family. In human bronchial epithelial cells the authors have shown that tumour necrosis factor (TNF)-alpha induced a significant decrease of E-cadherin and beta-catenin expression. The addition of dexamethasone inhibited this decrease. The aim of the present study was to investigate the effect of TNF-alpha and dexamethasone on the regulation of E-cadherin, gamma-catenin and beta-catenin in human nasal epithelial cells (HNEC). A primary culture of HNEC, obtained from human nasal turbinates after surgery, was used. The quantitative and qualitative modulation of E-cadherin, gamma-catenin and beta-catenin expression was assessed by Western blot and immunofluorescence analysis. In order to assess the TNF-alpha-induced activation of HNEC, interleukin-8 and RANTES (regulated on activation, normal T-cell expressed and secreted) release was assessed by enzyme-linked immunosorbent assay. The results showed that TNF-alpha induced, a decrease in gamma-catenin and beta-catenin expression, but had no effect on E-cadherin expression. Immunofluorescence showed that TNF-alpha induced cytoplasmic localisation of E-cadherin, gamma-catenin and beta-catenin. Dexamethasone inhibited the effect of TNF-alpha and induced a three-fold increase in E-cadherin expression. These results suggest that the difference in nasal and bronchial epithelial cohesion may be due to the differential effect of tumour necrosis factor-alpha and dexamethasone on E-cadherin expression.

Inhibition of mediator and cytokine release from dispersed nasal polyp cells by mizolastine.

BACKGROUND: Mizolastine is a potent and selective H1-receptor antagonist with antiallergic properties; in in-vitro animal models, mizolastine was shown to inhibit 5-lipoxygenase activity and to decrease the release of leukotrienes (LT) and tumor necrosis factor-alpha (TNF-alpha). This study investigated the effects of three concentrations of mizolastine (0.1, 1.0, 10 microM) on the release of LT (LTB4 and LTC4/D4) and prostaglandin D2 (PGD2) after stimulation by anti-IgE, and on the spontaneous release of cytokines (TNF-alpha and granulocyte/macrophage-colony-stimulating factor [GM-CSF]), from dispersed cells obtained from surgically resected nasal polyps of patients with nasal polyposis. METHODS: Cells from nasal polyps were obtained using enzymatic dispersion. For experiments involving the measurement of LT and PGD2, the cells were preincubated with mizolastine or its dissolution vehicle for 20 min prior to challenge with 10 microg/ml epsilon-chain specific anti-IgE for 45 min at 37 degrees C; for the cytokine release, cells were incubated with mizolastine or its dissolution vehicle for 24 h. LT and PGD2 were measured by enzyme immunoassay (EIA) and cytokines by enzyme-linked immunosorbent assay (ELISA) using commercially available kits. RESULTS: Mizolastine inhibited significantly and in a dose-dependent manner the release of LTB4 and TNF-alpha at all concentrations, LTC4/D4 at 10 microM, and GM-CSF from 1 microM; no effect was observed on the release of PGD2. CONCLUSION: Mizolastine inhibits the release of LT, TNF-alpha and GM-CSF in this in vitro model, which mimics closely the inflammatory cells of allergic rhinitis.

Fel d 1 production in the cat skin varies according to anatomical sites.

BACKGROUND: Fel d 1 is the major cat allergen, inducing asthma in sensitized individuals. It is produced by the skin and lies on fur. Recently, it was established that the amount of Fel d 1 on fur varies among anatomical sites. However, it is not known whether the allergen production by skin varies in parallel. The objective was to compare the Fel d 1 production by male cat skin in two anatomical sites, the face and the chest, in order to correlate it with Fel d 1 amounts on fur, and to assess the reaccumulation of Fel d 1 after washing. METHODS: Ten intact male cats were shaved under general anesthesia at both areas, and the fur was collected. The skin was washed and the washing fluid collected for Fel d 1 assays. Fel d 1 levels were measured in microg/g fur and ng/cm2 skin by ELISA before and after washing and 48 h later. RESULTS: In skin washing, the mean Fel d 1 level was significantly higher in the face (1015.2 +/- 821.6 ng/cm2) than the chest (115.2 +/- 66.8 ng/cm2). In the fur, the respective levels were 63.6 +/- 34 and 29.6 +/- 13.6 microg/g. In the skin sample taken after skin washing, the level of Fel d 1 dropped to 25.1 +/- 25.7 ng/cm2 on the face and to 22 +/- 17.4 ng/cm2 on the chest. After 2 days, skin Fel d 1 levels returned to basal values, with higher values on the face than the chest. CONCLUSIONS: This study shows that Fel d 1 levels on the skin are dramatically higher on the facial area than chest. This anatomical variation is concordant with the levels of Fel d 1 found on fur. Washing reduces levels of major allergen on cat skin and fur, but the accumulation on skin is restored within 2 days.