Periostin is required for maximal airways inflammation and hyperresponsiveness in mice

Abstract

Background Periostin, a secreted extracellular matrix protein, has been localized to deposits of subepithelial fibrosis in asthma, and periostin levels have been linked to elevation of IL-13. Objective We hypothesized that periostin is required for airway inflammatory responses to a physiologic aeroallergen, house dust mite (HDM). Methods We studied F4-F6 B6;129-Postntm1Jmol/J wild-type (+/+) and null (−/−) mice as well as C57BL/6 mice treated with either IgM or OC-20 periostin neutralizing antibody. Mice were exposed to five doses of HDM intranasally over a 16 day period. Results HDM increased airways responsiveness in Postn wild-type but not null mice. In addition, HDM-treated C57BL/6 mice injected with OC-20 had a lower airways responsiveness than HDM-treated mice injected with IgM. Compared to Postn wild-type mice, Postn null mice showed decreases in HDM-induced inflammation and mucous metaplasia, as well as reduced IL-4, IL-25, CD68, Gob5 and periostin mRNA expression. OC-20 antibody gave similar results. HDM exposure increased periostin expression in the airway epithelium, subepithelium, smooth muscle and inflammatory cells. OC-20 blocked the HDM-induced IgE response, and T cells incubated with dendritic cells (DCs) from Postn null mice or treated with OC-20 showed deficient DNA synthesis and IL-13 responses compared to T cells incubated with wild-type DCs. Finally, adoptive transfer of bone marrow-derived DCs from periostin wild-type mice was sufficient to promote allergic responses in F6 periostin null littermates. Conclusions In mice, periostin is required for maximal airways hyperresponsiveness and inflammation following HDM sensitization and challenge. Periostin is required for maximal HDM-induced T cell responses.

Periostin in bronchial asthma – a brief update

“…It appears that periostin enhanced expression is responsible for the induction of eosinophils recruitment in bronchial wall [12] and its ability to act as α v β 3 , α v β 5 , α 4 β 6 , and α M β 2 (CD11b) integrin ligand increases eosinophils adherence to fibronectin [25][26][27].…”

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

“…Некоторые исследователи в эксперименте на периостиндефицитных мышах показали, что этот белок действует как защитная молекула против аллергического воспаления дыхательных путей [43]. В других экспери-ментальных работах была найдена связь периостина с более тяжелым воспалением в респираторном тракте и более выраженной гиперреактивностью бронхов [44].…”

Periostin as a biomarker of airway inflammation

“…Normal lung development involves coordinated periostin expression, 8 and experimental models using periostin gene-deleted mice show that periostin is required for normal wound repair 9 and contributes to the pathogenic remodeling in a variety of chronic diseases including broncho-pulmonary dysplasia, bleomycin-induced fibrosis, atherosclerosis, inflammatory bowel disease, and asthma. 10 The serum periostin concentration as a systemic biomarker of local remodeling is increased in idiopathic pulmonary fibrosis 7 and predicts disease progression.…”

“…Periostin binding to αVβ3 integrins can activate Akt/PKB signaling to increase cell survival and can activate nuclear factor κB signaling, which is essential for many immune cell functions, particularly dendritic cells (DCs). Experimental allergic airway inflammation using house dust mite allergen was reduced in a postn -/-mouse model and this was partly rescued by passive transfer of wild-type postn-sufficient DCs, 10 suggesting that periostin may have an immunoregulatory function by providing a matricellular platform for lymphocyte interactions.…”

“…Possible interventions could include humanized periostin-neutralizing antibody, equivalent to OC-20 monoclonal antibodies, replicating postn -/-mice that have reduced pathogenic remodeling in experimental asthma. 10 Other therapeutics could include the vitamin D analog 22-oxacalcitriol, which might be effective by inhibition of Th2 cytokine-and TGFβ-induced POSTN expression or aptamers that bind to periostin and antagonize its interaction with integrins and inhibit adhesion and migration. 19 …”