Club cell 10-kDa protein attenuates airway mucus hypersecretion and inflammation.
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<0.05). CC10 at 20 ng·mL(-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.
Dept of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Erika
E
Tokita
Dept of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Tsuyoshi
T
Tanabe
Division of Physiology, School of Nursing and Rehabilitation Sciences, Showa University, Yokohama, Japan.
Kazuhito
K
Asano
Dept of Otorhinolaryngology, School of Medicine, Showa University, Tokyo, Japan.
Harumi
H
Suzaki
Dept of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA brubin@vcu.edu.
Bruce K
BK
Rubin
D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology*; D014598:Uteroglobin / Q000494:pharmacology*
D016207:Cytokines; D008070:Lipopolysaccharides; C556389:SCGB1A1 protein, human; D014598:Uteroglobin