Inhibition of IL-13-induced periostin in airway epithelium attenuates cellular protein expression of MUC5AC.

Suzaki I1,2, Kawano S1, Komiya K1, Tanabe T1, Akaba T1, Asano K3, Suzaki H4, Izuhara K5, Rubin BK1
Source: Respir Res
Publication Date: ()
Issue: 22: 93-100
Cells used in publication:
Epithelial, bronchial (NHBE), human
Species: human
Tissue Origin: lung



Serum periostin is increased in asthma and serves as a surrogate marker for IL-13 activity in the lung. Serum levels of periostin are the most robust biomarker predicting a favourable response to the anti-IL-13 drug, lebrikizumab. We investigated the mechanisms of IL-13 stimulation of periostin, the polarized secretion of periostin and whether periostin would have a direct effect on mucin secretion by airway cells.


Normal human bronchial epithelial (NHBE) cells were cultured at air-liquid interface (ALI) in the presence of IL-13, and we evaluated the effect of the specific inhibitors, leflunomide (Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) inhibitor) or PD98059 (MEK/extracellular regulated protein kinase (ERK) inhibitor), on periostin production. We examined MUC5AC secretion from NHBE cells exposed to recombinant human (rh) periostin or IL-13 in the presence and absence of OC-20, a periostin-neutralizing antibody.


IL-13 induced periostin protein which was predominantly secreted towards the basal surface of the cells. Periostin production was much greater from goblet cells than ciliated cells (P?<?0.001). Periostin production after exposure to IL-13 was attenuated by both leflunomide (P?<?0.001) and PD98059 (P?<?0.001). The addition of exogenous periostin modestly increased MUC5AC secretion (P?<?0.01), but did not visibly change cell morphology. IL-13-induced MUC5AC secretion was attenuated by OC-20 (P?<?0.01).


Periostin production in differentiated airway cells is mediated by JAK/STAT6 and MEK/ERK pathways. Periostin secretion is much greater from immunologically active goblet cells. IL-13-driven mucin production is partially inhibited by OC-20