Involvement of Periostin in Subepithelial Fibrosis of Bronchial Asthma Downstream of IL-4 and IL-13 Signals

摘要

Background: Subepithelial fibrosis is a cardinal feature of bronchial asthma. Collagen I, III, and V; fibronectin; and tenascin-C are deposited in the lamina reticularis. Extensive evidence supports the pivotal role of IL-4 and IL-13 in subepithelial fibrosis, however, the precise mechanism remains unclear. We have previously identified the POSTN gene encoding periostin as an 1L-4/IL-13-inducible gene in bronchial epithelial cells. Periostin is thought to be an adhesion molecule because it possesses four fasciclin I domains. Here, we explore the possibility that periostin is involved in subepithelial fibrosis in bronchial asthma. Methods: We have analyzed induction of perioslin in lung fibroblasts by IL-4 or IL-13. We next analyzed expression of periostin in asthma patients and in OVA-sensitized and inhaled mice. Furthermore, we examined the binding ability of periostin to other extracellular matrix proteins. Results: Both IL-4-and IL-13-induced secretion of periostin in lung fibroblasts independently of TGF-beta. Periostin co-localized with other extracellular matrix proteins involved in subepithelial fibrosis in both asthma patients and OVA-sensitized and inhalation challenged wild-type mice, but not in either IL-4 or IL-13 knockout mice. Perioslin had an ability to bind to fibronectin, tenascin-C, collagen V, and periostin itself. Conclusion: Periostin secreted by lung fibroblasts in response to IL-4 and/or IL-13 is a novel component of subepithelial fibrosis in bronchial asthma. Periostin may contribute to this process by binding to other extracellular matrix proteins.