To further understand the molecular mechanism of glucocorticoid action on gene expression, DNA-binding activities of the cis-acting transcription factors activator protein 1 (AP1), AP2, Egr1 (zif268), NF-B, the signal transducers and activators of transcription proteins gamma interferon activation site (GAS), Sis-inducible element, and the TATA binding protein transcription factor II D (TFIID) were examined in human epidermal keratinocytes. The cytokine interleukin 1␤ (IL-1␤) and platelet-activating factor (PAF), both potent mediators of inflammation, were used as triggers for gene expression. Budesonide epimer R (BUDeR) and dexamethasone (DEX) were studied as potential antagonists. BUDeR or DEX before IL-1␤-or PAF-mediated gene induction elicited strong inhibition of AP1-, GAS-, and in particular NF-B-DNA binding (P < 0.001, ANOVA). Only small effects were noted on AP2, Egr1 (zif268), and Sis-inducible element-DNA binding (P > 0.05). No significant effect was noted on the basal transcription factor TFIID recognition of TATA-containing core promoter sequences (P > 0.68). To test the hypothesis that changing cis-acting transcription factor binding activity may be involved in inflammatoryresponse related gene transcription, RNA message abundance for human cyclooxygenase (COX)-1 and -2 (E.C.1.14.99.1) was assessed in parallel by using reverse transcription-PCR. Although the COX-1 gene was found to be expressed at constitutively low levels, the TATA-containing COX-2 gene, which contains AP1-like, GAS, and NF-B DNA-binding sites in its immediate promoter, was found to be strongly induced by IL-1␤ or PAF (P < 0.001). BUDeR and DEX both suppressed COX-2 RNA message generation; however, no correlation was associated with TFIID-DNA binding. These results suggest that on stimulation by mediators of inflammation, although the basal transcription machinery remains intact, modulation of cis-activating transcription factor AP1, GAS, and NF-B-DNA binding by the glucocorticoids BUDeR and DEX play important regulatory roles in the extent of specific promoter activation and hence the expression of key genes involved in the inflammatory response.Glucocorticosteroids (GCs) have long been used therapeutically as immunosuppressive and anti-inflammatory agents; however, the mechanism of their activity is only recently becoming understood at the genetic level. GCs interact with an intracellular GC receptor, which subsequently translocates to the nucleus as a ligand-activated transcriptional modulator. In turn, the GC receptor regulates the expression of genes such as those encoding cytokines, matrix metalloproteinases, and cell adhesion molecules known to be critical to both inflammation and the immune response (1, 2). Besides a direct "type 1" interaction with a palindromic GC responsive element in GC-sensitive gene promoters (3, 4), functions of the GC receptor also include a "type 2" interaction with chromatin-associated cis-acting transcription factors. For example, the GC receptor can physically interact with the Fos and J...

It is well known that workers occupationally exposed to grain dust have a high prevalence of respiratory symptoms, but their pathogenesis remains obscure when sensitization to cereal flour cannot be demonstrated. Storage mites, tenebroids, and cockroaches are stored-grain pests found in grain and cereal products frequently in our area, where the cereal industry is the most important industry. An epidemiological analysis of sensitization of these stored-grain pests was performed on 4379 patients residing in an area of cereal industries. Fifty grain workers were selected for in vivo diagnostic tests with nine genera of mites, Tenebrio molitor and Blatta orientalis. Specific IgE antibodies to the extracts were demonstrated by prick tests and RAST. Association between respiratory symptoms and occupational exposure was confirmed by challenge tests (specific and methacholine). The prevalence of mite sensitization in the total sample studied (4379) was 18.96% (SEM 0.58, 95% CI 16.93-19.19). The prevalence of sensitization to storage mites among mite-sensitive patients was 11.88% (SEM 1.15, 95% CI 9.63-14.3). Among the 50 selected patients the most frequent sensitization was that to Dermatophagoides pteronyssinus (58%), followed by Dermatophagoides frinae (48%), Lepidoglyphus destructor and Tyrophagus putrescentiae (38%), Blomia kulagini (34%), and Acarus siro and Chortoglyphus arcuatus (24%). In addition, 22% of the patients presented negative prick tests and RAST for Dermatophagoides species with positive test to storage mites. Fifty percent of the 50 patients were sensitizated to Tenebrio molitor (SEM 0.7, CI 95% 36-64), and 36% to Blatta orientalis (SEM 0.67, CI 95% 23-49). The identification of mites, tenebroids, and cockroaches in dust samples yields useful data for the diagnosis of our patients.

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Prevalence of allergy to fungi is around 3–10%. The most prevalent species involved in sensitizations are Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, and Penicillium notatum. Our main objective was to estimate the prevalence of fungal sensitization and its variation across Spain. Following the ICH-GCP, we recruited 1156 patients from 15 allergy departments in Spain. Hospitals were selected by bioclimatic areas. Patients underwent a skin prick test (SPT) with fungi, pollens, house dust mites, and animal dander. Specific IgE to Alternaria alternata and Alt a 1 was assessed in patients with positive SPT to fungi. Of the 233 patients (20.2%) sensitized to at least one of the five fungi tested, 162 (69.5%) were sensitized to Alternaria alternata and Alt a 1, of whom 113 (69.8%) were children; 181 (77.7%) were also polysensitized to other allergens. Alternaria alternata and Alt a 1 sensitization was present in 25.4% of patients in the Continental area, 12.0% in the Mediterranean area, 7.0% in the Semidesertic area, and 2.3% in the Oceanic area. Prevalence of sensitization to the other tested sources was 63.8% to pollens, 60.5% to house dust mite, and 38.1% to animal dander. We concluded that the prevalence of fungal allergy is increasing. Fungi are still the fourth source of allergen sensitization. Alternaria alternata sensitization is the most prevalent in allergic patients to fungi. Alt a 1 is present in almost 90% of the patients sensitized to Alternaria alternata.

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