CC16 levels correlate with cigarette smoke exposure in bronchial epithelial cells and with lung function decline in smokers

Lam, David Chi‐Leung; Kwok, Hoi‐Hin; Yu, Wai‐Cho; Ko, Fanny W.; Tam, Cheuk‐Yin; Lau, Arthur Chun‐Wing; Fong, Daniel Yee Tak; Ip, Mary S.M.

doi:10.1186/s12890-018-0607-7

Cited by 20 publications

(24 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, modulation of inflammation via CC16 might provide a new therapeutic strategy for balancing inflammation. Interestingly, these studies suggest a putative role of bronchial CC16 against smoke-associated lung damage [38]. In our model, the anti-inflammatory effects of CC16 have been confirmed in the CLP-induced ALI upon blunt chest trauma.…”

Section: Discussionsupporting

confidence: 65%

“…These results are confirmed by the review of Laucho-Contreras et al showing that the high expression of CC16 was associated with a reduced inflammation and cellular injury in mice [14]. In patients suffering from pulmonary morbidities such as COPD or Asthma, CC16 is known to play a pivotal role in the pathological course and has a putative protective function during cigarette-smoke exposure [14,38]. Therefore, modulation of inflammation via CC16 might provide a new therapeutic strategy for balancing inflammation.…”

Section: Discussionmentioning

confidence: 64%

See 1 more Smart Citation

Early Local Inhibition of Club Cell Protein 16 Following Chest Trauma Reduces Late Sepsis-Induced Acute Lung Injury

Störmann

Becker

Vollrath

et al. 2019

JCM

View full text Add to dashboard Cite

Blunt thoracic trauma (TxT) deteriorates clinical post-injury outcomes. Ongoing inflammatory changes promote the development of post-traumatic complications, frequently causing Acute Lung Injury (ALI). Club Cell Protein (CC)16, a pulmonary anti-inflammatory protein, correlates with lung damage following TxT. Whether CC16-neutralization influences the inflammatory course during ALI is elusive. Ninety-six male CL57BL/6N mice underwent a double hit model of TxT and cecal ligation puncture (CLP, 24 h post-TxT). Shams underwent surgical procedures. CC16 was neutralized by the intratracheal application of an anti-CC16-antibody, either after TxT (early) or following CLP (late). Euthanasia was performed at 6 or 24 h post-CLP. Systemic and pulmonary levels of IL-6, IL-1β, and CXCL5 were determined, the neutrophils were quantified in the bronchoalveolar lavage fluid, and histomorphological lung damage was assessed. ALI induced a significant systemic IL-6 increase among all groups, while the local inflammatory response was most prominent after 24 h in the double-hit groups as compared to the shams. Significantly increased neutrophilic infiltration upon double hit was paralleled with the enhanced lung damage in all groups as compared to the sham, after 6 and 24 h. Neutralization of CC16 did not change the systemic inflammation. However, early CC16-neutralization increased the neutrophilic infiltration and lung injury at 6 h post-CLP, while 24 h later, the lung injury was reduced. Late CC16-neutralization increased neutrophilic infiltration, 24 h post-CLP, and was concurrent with an enhanced lung injury. The data confirmed the anti-inflammatory potential of endogenous CC16 in the murine double-hit model of ALI.

show abstract

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 64%

Early Local Inhibition of Club Cell Protein 16 Following Chest Trauma Reduces Late Sepsis-Induced Acute Lung Injury

Störmann

Becker

Vollrath

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…The report from David Chi-Leung Lam et al showed a relationship between low serum CC16 levels at baseline and greater lung function decline over the course of 10 years in a Chinese longitudinal cohort. In that study, they also found that the level of CC16 mRNA in endoscopic biopsies of the bronchial epithelium was also correlated with the FEV1/FVC ratio [30]. Compared to endoscopic biopsies of bronchial epithelium, the induction of sputum production and subsequent detection of CC16 mRNA in our study was less invasive and more practical.…”

Section: Discussionsupporting

confidence: 65%

“…Recent studies have shown that epithelial cell damage and airway remodeling result in the reduction of the level of CC16 in patients with COPD [29]. Most previous studies have indicated that serum CC16 levels are related to functional declines in COPD patients; however, few studies have focused on sputum CC16 levels [30,31]. We found a signi cantly lower level of CC16 mRNA in patients with severe and extremely severe COPD than in those with mild and moderate COPD, suggesting that that CC16 in the lower airways may contribute to the progressive anatomical damage in the end stage of COPD.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Biomarkers in induced Sputum Predict Chronic Obstructive Pulmonary Disease (COPD) Severity

He¹,

Deng²,

Jia³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The progression of an abnormal inflammatory response plays a crucial role in the functional decline that occurs in COPD patients[1].Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of the inflammatory processes in the airways. Based on this, we explored the association of inflammatory biomarkers in induced sputum with lung function in COPD patients.Methods: 102 patients with COPD were recruited and underwent spirometry. According to the percentage of the predicted forced expiratory volume in 1 second value (FEV1%pred), participants with COPD were divided into a mild and moderate group (FEV1%pred≥ 50%, n=57) and a severe and extremely severe group (FEV1%pred<50%, n=45). Then we analyzed a series of inflammatory biomarkers in induced sputum and determined their association with lung function in COPD patients.Results: We found an increased levels of eosinophils percentage, MMP9 mRNA, LTB4R mRNA, and decreased levels of CC16 mRNA and miR-155 in the induced sputum of patients with severe and extremely severe COPD. In our analysis, sputum cell CC16 mRNA expression, but not CC16 secretion in the supernatant of the sputum, was closely and independently correlated with lung function decline in patients with COPD. Conclusion: The levels of numerous inflammatory biomarkers in induced sputum were associated with lung function decline in COPD，and the relative CC16 mRNA expression level with a cutoff of 1.09 could be a predictive biomarker of the severity of COPD.

show abstract

“…Furthermore, lung inflammation induced by cigarette smoke and adverse outcomes were ameliorated by CC16 in a murine COPD model ( 32 , 33 ). Of note, in patients with pulmonary morbidities, including COPD and asthma, CC16 plays an important role in pathology and performs protective functions during exposure to cigarette smoke ( 33 , 49 ). Although reduced lung damage following CC16 neutralization was observed, the general mortality rate did not change in the current model.…”

Section: Discussionmentioning

confidence: 99%

Early local neutralization of CC16 in sepsis‑induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival

et al. 2020

View full text Add to dashboard Cite

Blunt thoracic trauma (TxT) is a common injury pattern in polytraumatized patients. When combined with a secondary trigger, TxT often results in acute lung injury (ALI), which negatively affects outcomes. Recent findings suggest that ALI is caused by both local and systemic inflammatory reactions. Club cell protein (CC)16 is an anti-inflammatory peptide associated with lung injury following TxT. Recently, the anti-inflammatory properties of endogenous CC16 in a murine model of TxT with subsequent cecal-ligation and puncture (CLP) as the secondary hit were demonstrated by our group. The present study aimed to determine whether CC16 neutralization improves survival following 'double-hit'-induced ALI. For this purpose, a total of 120 C57BL/6N mice were subjected to TxT, followed by CLP after 24 h. Sham-operated animals underwent anesthesia without the induction of TxT + CLP. CC16 neutralization was performed by providing a CC16 antibody intratracheally following TxT (early) or following CLP (late). Survival was assessed in 48 animals for 6 days after CLP. Sacrifice was performed 6 or 24 h post-CLP to evaluate the anti-inflammatory effect of CC16. The results revealed that CC16 neutralization enhanced pro-inflammatory CXCL1 levels, thereby confirming the anti-inflammatory characteristics of CC16 in this model. Early CC16 neutralization immediately following TxT significantly prolonged survival within 60 h; however, the survival rate did not change until 6 days post-trauma. Late CC16 neutralization did not provide any survival benefits. On the whole, the present study demonstrated that neutralizing CC16 confirmed its anti-inflammatory potential in this double-hit ALI model. Early CC16 neutralization prolonged survival within 60 h; however, no survival benefits were observed after 6 days post-CLP in any group.

show abstract

CC16 levels correlate with cigarette smoke exposure in bronchial epithelial cells and with lung function decline in smokers

Cited by 20 publications

References 28 publications

Early Local Inhibition of Club Cell Protein 16 Following Chest Trauma Reduces Late Sepsis-Induced Acute Lung Injury

Early Local Inhibition of Club Cell Protein 16 Following Chest Trauma Reduces Late Sepsis-Induced Acute Lung Injury

Inflammatory Biomarkers in induced Sputum Predict Chronic Obstructive Pulmonary Disease (COPD) Severity

Early local neutralization of CC16 in sepsis‑induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival

Contact Info

Product

Resources

About