Periostin up-Regulates the Effector Functions of Eosinophils

Abstract

Periostin, an extracellular matrix protein, is up-regulated in asthmatic airways, mainly by T helper (Th) 2 cytokines. Periostin functions as a matricellular protein in cell activation by binding to cell surface receptors. However, the role of periostin in the development of eosinophilic airway inflammation has not been fully clarified. Here, we examined whether periostin could modify eosinophil functions such as superoxide anion (O2−) generation, degranulation, and production of cytokine/chemokines. Eosinophils were isolated from the blood of healthy volunteers or allergic subjects, and their adhesion to recombinant human periostin was measured using eosinophil peroxidase assays. Eosinophil O2−generation was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by ELISA as a marker of degranulation, and concentrations of cytokine/chemokines were also measured. Periostin directly induces eosinophil adhesion, which was enhanced by IL-5. Periostin also activated other functions of eosinophils such as O2− generation and EDN release. Anti-αM or anti-β2 integrin monoclonal antibody suppressed the eosinophil adhesion, O2−generation, and EDN release induced by periostin. Finally, periostin increased the production of transforming growth factor (TGF-β)1, TGF-β2 and cysteinyl leukotrienes (cysLTs) from eosinophils. These findings suggested that periostin up-regulates eosinophil functions through αMβ2 integrin. These effects may be involved in the activation of eosinophils and in the development of remodeling in the airway of Th2-dominant asthma, and could possibly aggravate the disease.