Club cell 10-kDa protein attenuates airway mucus hypersecretion and inflammation
- 15 May 2014
- journal article
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 44 (4), 1002-1010
- https://doi.org/10.1183/09031936.00080913
Abstract
Bacterial lipopolysaccharide (LPS) and interleukin (IL)-13 increase mucus secretion and inflammatory cytokine production in normal human bronchial epithelial (NHBE) cells. We evaluated the effect of club cell 10-kDa protein (CC10), an anti-inflammatory protein produced by epithelial cells, on mucus secretion, cell morphology and inflammatory cytokine production. NHBE cells were cultured at an air–liquid interface with CC10 or vehicle and exposed to LPS on day 14. Mucin MUC5AC, IL-8 and granulocyte-macrophage colony-stimulating factor were measured in cell supernatants. MUC5AC and IL-8 mRNA expression were measured by real-time PCR. Western blotting was used to evaluate nuclear factor (NF)-κB and extracellular signal-regulated kinase (ERK) activation. Cells were evaluated histologically. Additionally, NHBE cells were exposed to IL-13 and CC10 for 14 days, and secretion of the mucins MUC5AC and MUC5B was measured. MUC5AC secretion stimulated either by LPS or by IL-13 was attenuated by CC10 at 20 ng·mL−1 (p−1 also attenuated IL-8 secretion (p<0.05). MUC5AC and IL-8 mRNA expression were also decreased by CC10 (p<0.05). CC10 attenuated phosphorylation of NF-κB (p<0.05) and ERK1/2 (p<0.05). CC10 attenuates LPS-induced mucus secretion in airway cells, in part due to inhibition of NF-κB and ERK phosphorylation.Keywords
This publication has 42 references indexed in Scilit:
- IL‐13‐inducedMUC5ACproduction and goblet cell differentiation is steroid resistant in human airway cellsClinical and Experimental Allergy, 2011
- Leptin up-regulates MUC5B expression in human airway epithelial cells via mitogen-activated protein kinase pathwayExperimental Lung Research, 2010
- Clara Cell 10-kD Protein Suppresses Chitinase 3-Like 1 Expression Associated with Eosinophilic Chronic RhinosinusitisAmerican Journal of Respiratory and Critical Care Medicine, 2010
- Changes in Clara Cell 10 kDa Protein (CC10)-positive Cell Distribution in Acute Lung Injury Following Repeated Lipopolysaccharide Challenge in the RatToxicologic Pathology, 2008
- Structure and Function of the Polymeric Mucins in Airways MucusAnnual Review of Physiology, 2008
- Modulation of mucus production by interleukin‐13 receptor α2 in the human airway epitheliumClinical and Experimental Allergy, 2007
- Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cellsJournal of Allergy and Clinical Immunology, 2007
- Inverse relation between nasal fluid Clara Cell Protein 16 levels and symptoms and signs of rhinitis in allergen‐challenged patients with intermittent allergic rhinitisAllergy, 2007
- Lipopolysaccharide-induced down-regulation of uteroglobin in the human noseActa Oto-Laryngologica, 2007
- Uteroglobin inhibits phospholipase A2 activityLife Sciences, 1986