Role of club cell 16-kDa secretory protein in asthmatic airways

Club cell 16-kDa secretory protein (CC16) is a pneumoprotein and functions as an anti-inflammatory or antioxidant protein. However, altered levels of serum CC16 as well as their effect on airways inflammation have not been fully evaluated.

We recruited 63 adult asthmatics on maintenance medications and 61 healthy controls (HCs). The asthmatic subjects were divided into two groups according to the result of bronchodilator responsiveness (BDR) test: the present BDR (n = 17) and absent BDR (n = 46) groups. Serum CC16 levels were measured by ELISA. As an in vitro study, the effect of Dermatophagoides pteronyssinus antigen 1 (Der p1) on the production of CC16 in airways epithelial cells (AECs) according to a time-dependent manner was assessed; the effects of CC16 protein on oxidative stress system, airways inflammation and remodelling were tested.

Serum CC16 levels showed significantly higher in the asthmatics than in the HCs (p < .001) with a positive correlation with FEV₁ % (r = .352, p = .005). The present BDR group had significantly lower levels of serum CC16, FEV₁ % and MMEF%, but showed higher level of FeNO than the absent BDR group. Serum CC16 levels (below 496.0 ng/mL) could discriminate the present BDR group from the absent BDR group (area under the curve = 0.74, p = .004). In vitro testing demonstrated that Der p1 exposure significantly induced CC16 release from AECs for 1 h, which was progressively decreased after 6 h and followed by MMP-9 and TIMP-1 production. These findings were associated with oxidant/antioxidant disequilibrium and restored by CC16 treatment (but not dexamethasone).

Decreased CC16 production contributes to persistent airways inflammation and lung function decline. CC16 may be a potential biomarker for asthmatics with BDR.