Club cell 10-kDa protein attenuates airway mucus hypersecretion and inflammation

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)-kB 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-kB (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-kB and ERK phosphorylation. @ERSpublications CC10 attenuates LPS-induced mucus secretion in airway cells and plays a role in decreasing airway inflammation

Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After Lower Respiratory Tract Infections in Infancy

“…43,44 Following acute viral infections, transgenic mice deficient in CC16 develop a more severe lung inflammation with increased Th2 cytokine levels, airway reactivity, and mucous production, as well as prolonged viral persistence. 45,46 Reconstitution of CC16 in mice is able to reverse these altered phenotypes.…”

Club cells and CC16: another “smoking gun”? (With potential bullets against COPD)

“…CC16 polymorphism and local deficiency on the one hand, and a decreased number of club cells on the other hand, were reported as features of COPD [8,9], as confirmed by LAUCHO-CONTRERAS et al [10] in the current issue of the European Respiratory Journal. In previous studies, exogenous CC16 showed pharmacological properties that could decrease excess airway inflammation and mucus production in ex vivo models [11][12][13]. However, CC16 has not demonstrated physiological properties, as shown in a prior report on CC16-deficient mice, which were not more susceptible to changes induced by cigarette smoke [14].…”

Club cells, CC10 and self-control at the epithelial surface

“…The study by TOKITA et al [10] adds to the body of evidence showing that CC10, at physiologically relevant concentrations, may contribute to the maintenance of homeostasis in the peripheral airways. Does this also mean that CC10 is a candidate drug for the treatment of inflammatory lung diseases?…”

“…In this issue of the European Respiratory Journal, TOKITA et al [10] provide evidence that CC10 may also inhibit mucus secretion by lipopolysaccharide-or IL-13-exposed human primary bronchial epithelial cells. They cultured these cells at the air-liquid interface to allow mucociliary differentiation, and showed that CC10 at 20 ng?mL -1 inhibited secretion and mRNA expression of both the mucin MUC5AC and the neutrophil chemoattractant IL-8/CXCL8.…”