The results suggest that endogenous glucocorticoids may play a significant role in the modulation of airway responses to antigen challenge, and that antigen challenge may induce cortisol production in allergic subjects.
Summary:A 39 year old man who presented with classical Henoch-Schonlein purpura wasshown to have mediastinal nodular sclerosing Hodgkin's lymphoma. The Henoch-Schonlein purpura resolved after treatment of the lymphoma.
RATIONALE: Exposures to fungal bioaerosols have been associated with respiratory morbidities. The mechanisms that underlie the pulmonary immune response to Stachybotrys chartarum requires further characterization. Here we examine the murine pulmonary microRNA (miRNA), mRNA, and proteomic profiles following S. chartarum subchronic inhalation exposures. METHODS: Female B6C3F1/N mice (n55-7) repeatedly inhaled viable S chartarum conidia (3x10 4 total) or HEPA-filtered air twice a week for 4 and 13 weeks. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected at 24 and 48 hours following final exposure and processed for RNA, proteomic, and flow cytometry analyses. RESULTS: Proteomic analysis showed a significant increase in chitinaselike proteins known to be associated with asthma. BALF cellularity revealed a Th2 response dominated by increased CD4+ T cells, IL-4, and IL-13 at 4 weeks that shifted to an IFNg + Th1 dominant response after 13 weeks. Macrophages were elevated after 4 and 13 weeks of exposure, along with increased arg1, retnla and il33 expression, indicating ongoing inflammation. Eosinophil levels were dramatically increased after 4 weeks but were decreasing by 13 weeks, potentially attributed to increased ccl11 and cxcl5, genes mediated by TNF. Interestingly, miR-21a, known to regulate tnf, was the only miRNA upregulated in whole lung homogenate 48 hours post 13 week exposure. CONCLUSIONS: These datasets support a chronic inflammatory response with a mixed T cell response that shifts from an early Th2 response after 4 weeks of exposure toward a more Th1 dominant response after 13 weeks of subchronic inhalation exposure to S chartarum conidia.
Abstracts AB75
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