In Vivo Allergen-Activated Eosinophils Promote Collagen I and Fibronectin Gene Expression in Airway Smooth Muscle Cells via TGF-1 Signaling Pathway in Asthma.

Eosinophils infiltration and releasing TGF-1 in the airways has been implicated in the pathogenesis of asthma, especially during acute episodes provoked by an allergen. TGF-1 is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodeling in asthma. We aimed to evaluate the effect of in vivo allergen-activated eosinophils on the expression of and in ASM cells in asthma. A total of 12 allergic asthma patients and 11 healthy subjects were examined. All study subjects underwent bronchial challenge with allergen. Eosinophils from peripheral blood were isolated before and 24 h after the bronchial allergen challenge using high-density centrifugation and magnetic separation. Individual co-cultures of blood eosinophils and immortalized human ASM cells were prepared. The TGF-1 concentration in culture supernatants was analyzed using ELISA. Gene expression was analyzed using qRT-PCR. Eosinophils integrins were suppressed with linear RGDS peptide before co-culture with ASM cells. Results: The expression of in asthmatic eosinophils significantly increased over non-activated asthmatic eosinophils after allergen challenge, < 0.001. The TGF-1 concentration in culture supernatants was significantly higher in samples with allergen-activated asthmatic eosinophils compared to baseline, < 0.05. The effect of allergen-activated asthmatic eosinophils on the expression of , , and in ASM cells was more significant compared to non-activated eosinophils, < 0.05, however, no difference was found on expression. The incubation of allergen-activated asthmatic eosinophils with RGDS peptide was more effective compared to non-activated eosinophils as the gene expression in ASM cells was downregulated equally to the same level as healthy eosinophils.