IL-13 acidifies airway surface liquid pH via an omeprazole inhibitable mechanism
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Jin Young Min, MD PhD, Julia He Huang, MS, James E Norton, MS, Lydia A Suh, BS, Caroline PE Price, Roderick G. Carter, BS, Su Y Jung, Hyung S Kim, David B. Conley, MD, Stephanie Shintani-Smith, MD, Kevin C. Welch, MD, Anju T. Peters, MD FAAAAI, Leslie C. Grammer, MD FAAAAI, Whitney W. Stevens, MD PhD, Kathryn E. Hulse, PhD, Atsushi Kato, PhD, Robert C. Kern, MD, Robert P. Schleimer, PhD FAAAAI, Bruce K. Tan, MD, MS
RATIONALE: Airway surface liquid (ASL) acidification impairs host defense and has been observed in severe asthma and cystic fibrosis. We recently reported that type-2 cytokines induce an omeprazole inhibitable H,K-exchange via the nongastric H,K-ATPase in human nasal epithelial cells (HNECs). In this study, we evaluated if IL-13 acidifies ASL pH and whether omeprazole modulates this response in vitro. Furthermore, we identified whether ASL pH is altered in chronic rhinosinusitis with nasal polyps (CRSwNP) and whether it is associated with type-2 cytokines in nasal tissue in vivo.

METHODS: HNECs cultured at air-liquid interface were stimulated basally with 5ng/mL IL-13 in the presence or absence of omeprazole. Apical ASL pH was measured using a pH-sensitive SNARF-dextran dye. Nasal secretions were collected from control and CRS patients and pH was measured using a micro-pH meter. Inflammatory cytokine levels in nasal tissue from the same patients were assessed by Luminex assay.

RESULTS: The ASL pH from IL-13-stimulated HNECs (7.20±0.38) was significantly acidified compared to the ASL pH from unstimulated cells (7.39±0.32; P=0.03). Omeprazole prevented IL-13-induced acidification of ASL pH (7.39±0.35; P=0.004). Furthermore, the pH of nasal secretions was acidified in CRSwNP (6.16±0.54) compared to control (6.56±0.28; P=0.006) patients. Nasal secretion pH was significantly negatively correlated with type-2 cytokine levels, including IL-13, IL-4, and IL-5 (all p<0.05).

CONCLUSIONS: IL-13 acidified ASL pH in vitro and this was inhibited by omeprazole. Type-2-mediated inflammation in vivo was associated with acidified ASL pH in CRSwNP patients. Inhibition of IL-13-induced ASL pH acidification may provide therapeutic benefits to CRSwNP patients.