The immune modulation of Clara cell-10 in human peripheral monocytes and dendritic cells

BackgroundClub cell protein-16 (CC16) expression has been associated with smoking-related lung function decline. The study hypothesis was that CC16 expression in both serum and bronchial epithelium is associated with lung function decline in smokers, and exposure to cigarette smoke will lead to reduction in CC16 expression in bronchial epithelial cells.MethodsIn a cohort of community-based male Chinese subjects recruited for lung function test in 2000, we reassessed their lung function ten years later and measured serum levels of CC16. CC16 expression was further assayed in bronchial epithelium from endobronchial biopsies taken from an independent cohort of subjects undergoing autofluorescence bronchoscopy, and tested for correlation between CC16 immunostaining intensity and lung function. In an in-vitro model, bronchial epithelial cells were exposed to cigarette smoke extract (CSE), and the expression levels of CC16 were measured in bronchial epithelial cells before and after exposure to CSE.ResultsThere was a significant association between FEV1 decline and serum CC16 levels in smokers. Expression of CC16 in bronchial epithelium showed significant correlation with FEV1/FVC. Bronchial epithelial cells showed significant decrease in CC16 expression after exposure to CSE, followed by a subsequent rise in CC16 expression upon removal of CSE.ConclusionsResults of these clinical and laboratory investigations suggested that low serum CC16 was associated with smoking-related decline in lung function, demonstrated the first time in a Chinese cohort. The data also lend support to the putative role of CC16 in protection against smoking-related bronchial epithelial damage.(Abstract word count: 243)US clinical trial registryNCT01185652, first posted 20 August, 2010.

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

Lam

Kwok

Yu³

et al. 2018

BMC Pulm Med

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Inhibition of COX-2 ameliorates murine liver schistosomiasis japonica through splenic cellular immunoregulation

Zhang

Chen

et al. 2022

Parasites Vectors

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Background We have reported the positive association of the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) axis with liver fibrosis induced by Schistosoma japonicum (Sj) infection, and TLR4 signaling controlled this axis. However, how COX-2 regulates immune response during Sj infection is still unclear. Methods Hematoxylin and eosin staining was used to evaluate the effect of the COX-2-specific inhibitor NS398 on liver granulomatous inflammation and fibrosis. Flow cytometry was used to explore the frequency and amount of different immune cell infiltration in the spleen during Sj infection. Results NS398 significantly reduced the size of liver granuloma, spleen, and mesenteric lymph node (MLN) and alleviated chronic granulomatous inflammation. Mechanically, this might be by decreasing the number of Sj-induced macrophages and T helper type 1 (Th1), Th2, T follicular helper (Tfh), T follicular regulatory (Tfr), and germinal center B (GC B) cells. There were no differences in the number of neutrophils, myeloid-derived suppressor cells, Th17 cells, regulatory T cells (Treg), or total B cells in the spleen of the mice with or without NS398 treatment. Conclusions COX-2/PGE2 inhibition may represent a potential therapeutic approach for schistosomiasis japonica through splenic cellular immunoregulation. Graphical Abstract

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Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD)

Laucho-Contreras

Polverino

Tesfaigzi

et al. 2016

Expert Opinion on Therapeutic Targets

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Introduction Club cell protein 16 (CC16) is the most abundant protein in bronchoalveolar lavage fluid. CC16 has anti-inflammatory properties in smoke-exposed lungs, and chronic obstructive pulmonary disease (COPD) is associated with CC16 deficiency. Herein, we explored whether CC16 is a therapeutic target for COPD. Areas Covered We reviewed the literature on the factors that regulate airway CC16 expression, its biologic functions and its protective activities in smoke-exposed lungs using PUBMED searches. We generated hypotheses on the mechanisms by which CC16 limits COPD development, and discuss its potential as a new therapeutic approach for COPD. Expert Opinion CC16 plasma and lung levels are reduced in smokers without airflow obstruction and COPD patients. In COPD patients, airway CC16 expression is inversely correlated with severity of airflow obstruction. CC16 deficiency increases smoke-induced lung pathologies in mice by its effects on epithelial cells, leukocytes, and fibroblasts. Experimental augmentation of CC16 levels using recombinant CC16 in cell culture systems, plasmid and adenoviral-mediated over-expression of CC16 in epithelial cells or smoke-exposed murine airways reduces inflammation and cellular injury. Additional studies are necessary to assess the efficacy of therapies aimed at restoring airway CC16 levels as a new disease-modifying therapy for COPD patients.

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The immune modulation of Clara cell-10 in human peripheral monocytes and dendritic cells

Cited by 5 publications

References 28 publications

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

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

Inhibition of COX-2 ameliorates murine liver schistosomiasis japonica through splenic cellular immunoregulation

Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD)

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