Clara cell 16 protein in COPD sputum: A marker of small airways damage?

Braido, Fulvio; Riccio, Anna Maria; Guerra, Laura; Gamalero, Cinzia; Zolezzi, Alberto; Tarantini, Francesco; Giovanni, Barbara De; Folli, Chiara; Descalzi, Desideria; Canonica, Giorgio Walter

doi:10.1016/j.rmed.2007.05.023

Cited by 53 publications

(48 citation statements)

References 23 publications

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“…CC16 is not uniformly expressed in the respiratory tract but predominantly in trachea, bronchi, and terminal bronchioles (47,48), and sputum may be a more suitable specimen for reflecting circulating CC16. Contrary to CC16, SP-D is sparsely expressed in conducting airways (11). Poor correlation of blood protein level with mRNA expression level for SP-D has been well known (49), potentially related to post-transcriptional modification and half-life of this protein biomarker.…”

Section: Discussionmentioning

confidence: 99%

“…COPD may result from localized inflammation of the respiratory system and from systemic inflammatory insults. Clara cell secretory protein (CC16) and surfactant protein D (SP-D) are produced predominantly in the respiratory system (pneumoproteins) and have recently been related to COPD susceptibility and COPDrelated clinical phenotypes (10)(11)(12)(13)(14). Other systemic inflammatory markers including C-reactive protein (CRP), fibrinogen, IL-6, IL-8, and tumor necrosis factor (TNF)-a have also been reported to be associated with COPD risk, COPD mortality, COPD exacerbations, or lung function decline (15)(16)(17)(18).…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

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Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

Kim

Cho

Hersh

et al. 2012

Am J Respir Crit Care Med

113

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Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-a) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P , 1 3 10 28 ), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P ¼ 0.009-0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P ¼ 0.001-0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).

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Section: Discussionmentioning

confidence: 99%

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

Kim

Cho

Hersh

et al. 2012

Am J Respir Crit Care Med

113

View full text Add to dashboard Cite

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“…These changes seem to be related to pathogenesis of smokerelated lung diseases. We and others have found a further decrease in CC16 in COPD and its exacerbations [11,14,19,20]. However, in one study, healthy smokers had a relative high level of CC16 in the airways, with similar levels in bronchial fluids between smokers and non-smokers [21].…”

Section: Introductionmentioning

confidence: 77%

Sputum And Nasal Lavage Lung-Specific Biomarkers Before And After Smoking Cessation

Tsiligianni¹,

Bouloukaki²,

Tsoumakidou³

et al. 2011

C38. Airway Inflammation: From Mechanisms to Non-Invasive Biomarkers

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Background: Little is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation. Methods: Induced sputum and nasal lavage was obtained from healthy current smokers (n = 76) before smoking cessation, after 6 months of smoking cessation (n = 29), after 1 year of smoking cessation (n = 22) and from 10 healthy never smokers. SLPI, CC16, elafin and HBD-2 levels were measured in sputum and nasal lavage supernatants by commercially available ELISA kits.

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“…Moreover, primary cultures of neonatal pulmonary cells express Sca-1 and other stem cell markers, among which Clara cell secretion protein, suggesting that these cells represent a subpopulation of Clara cells implicated as lung stem/progenitor cells in lung injury models (21). Clara cells are believed to play a role not only in carcinogenesis but also in the pathogenesis of smoke-related chronic obstructive pulmonary diseases (22).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of stem cell antigen-1 in the lung of neonatal mice exposed to environmental cigarette smoke

et al. 2009

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Abstract. Mice are particularly susceptible to carcinogens when exposure starts early in life. We evaluated the expression of stem cell antigen-1 (Sca-1) gene in the lung of variously aged CD-1 mice, either untreated or exposed to environmental cigarette smoke (ECS) and/or to a light source. Sca-1 expression progressively decreased with age. The expression of Sca-1 gene and the amount of Sca-1 protein, which was exclusively localized in endothelial cells of the pulmonary vasculature, were significantly upregulated in mice exposed either to ECS or ECS plus light throughout the weaning period, starting at birth. These findings may contribute to explain the high vulnerability of mouse lung early in life.

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Clara cell 16 protein in COPD sputum: A marker of small airways damage?

Cited by 53 publications

References 23 publications

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

Sputum And Nasal Lavage Lung-Specific Biomarkers Before And After Smoking Cessation

Upregulation of stem cell antigen-1 in the lung of neonatal mice exposed to environmental cigarette smoke

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