Sputum Cathelicidin, Urokinase Plasminogen Activation System Components, and Cytokines Discriminate Cystic Fibrosis, COPD, and Asthma Inflammation

Xiao, Wei; Hsu, Yao‐Pi; Ishizaka, Akitoshi; Kirikae, Teruo; Moss, Richard B.

doi:10.1378/chest.128.4.2316

Cited by 133 publications

(149 citation statements)

References 56 publications

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“…Likewise, some studies reported greater IL-6 levels in sputum supernatant from COPD [4,14] while their sputum failed to release more IL-6 in our study. As for IFN-γ it was reported to be normal in sputum supernatant of COPD compared to healthy subjects [14,42]. It highlights the fact that sputum supernatant and sputum cell culture supernatant are not the same milieu.…”

Section: Discussionmentioning

confidence: 99%

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

Moermans¹,

Heinen

Nguyen

et al. 2011

Cytokine

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Background: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease caused by repeated exposure to noxious gases or particles. It is now recognized that the disease also features systemic inflammation. The purpose of our study was to compare airway and systemic inflammation in COPD to that seen in healthy subjects and to relate the inflammation with the disease severity. Methods: Ninety-five COPD patients, encompassing the whole severity spectrum of the disease, were recruited from our outpatient clinic and rehabilitation center and compared to 33 healthy subjects. Induced sputum and blood samples were obtained for measurement of inflammatory cell count. Interleukin (IL)-4, IL-6, IL-10, TNF-α and IFN-γ produced by 24 h sputum and blood cell cultures were measured. Results: Compared to healthy subjects, COPD exhibited a prominent airway neutrophilic inflammation associated with a marked IL-10, IL-6 and TNF-α release deficiency that contrasted with a raised IFN-γ production. Neutrophilic inflammation was also prominent at blood level together with raised production of IFN-γ, IL-10 and TNF-α. Furthermore, sputum neutrophilia correlated with disease severity assessed by GOLD stages. Likewise the extent of TNF-α release from blood cells also positively correlated with the disease severity but negatively with that of sputum cell culture. Blood release of TNF-α and IL-6 negatively correlated with body mass index. Altogether, our results showed a significant relationship between cellular marker in blood and sputum but poor relationship between local and systemic release of cytokines. Conclusions: COPD is characterized by prominent neutrophilic inflammation and raised IFN-γ production at both bronchial and systemic level. Overproduction of TNF-α at systemic level correlates with disease severity and inversely with body mass index.

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Section: Discussionmentioning

confidence: 99%

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

Moermans¹,

Heinen

Nguyen

et al. 2011

Cytokine

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“…Most studies addressing the mechanisms of CF airway disease pathogenesis have focused on epithelial cells and neutrophils (4,(45)(46)(47)(48)(49)(50). These cell types are important contributors to the altered airway environment.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus fumigatus Generates an Enhanced Th2-Biased Immune Response in Mice with Defective Cystic Fibrosis Transmembrane Conductance Regulator

Allard

Poynter

Marr

et al. 2006

The Journal of Immunology

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Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20–40% of CF patients and are of unclear clinical significance. In this study, we demonstrate that CF transmembrane conductance regulator (CFTR)-deficient (CFTR knockout, Cftrtm1Unc-TgN(fatty acid-binding protein)CFTR) and mutant (ΔF508) mice develop profound lung inflammation in response to Aspergillus fumigatus hyphal Ag exposure. CFTR-deficient mice also develop an enhanced Th2 inflammatory response to A. fumigatus, characterized by elevated IL-4 in the lung and IgE and IgG1 in serum. In contrast, CFTR deficiency does not promote a Th1 immune response. Furthermore, we demonstrate that CD4+ T cells from naive CFTR-deficient mice produce higher levels of IL-4 in response to TCR ligation than wild-type CD4+ T cells. The Th2 bias of CD4+ T cells in the absence of functional CFTR correlates with elevated nuclear levels of NFAT. Thus, CFTR is important to maintain the Th1/Th2 balance in CD4+ T cells.

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“…An increase in uPA levels is associated with numerous pathologies, such as asthma, COPD, and interstitial lung disease. [12][13][14] The uPA mechanism of various actions remains incompletely understood despite the association of uPA with several activities.…”

mentioning

confidence: 99%

Involvement of urokinase in cigarette smoke extract-induced epithelial–mesenchymal transition in human small airway epithelial cells

Wang

Zhang

et al. 2015

Laboratory Investigation

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Urokinase-type plasminogen activator (uPA) augments inflammation and tissue remodeling during lung injury and repair. The uPA expression in small airway epithelium of chronic obstructive pulmonary disease (COPD) increases. Epithelialmesenchymal transition (EMT) is important in the small airway fibrosis of COPD. This study shows the uPA regulation in cigarette smoke extract (CSE)-induced EMT in human small airway epithelial cell lines (HSAEpiCs). uPA is overexpressed in the small airway epithelium of COPD patients and CSE-treated cell lines. Furthermore, uPA expression correlated with vimentin expression in the small airway epithelium of COPD patients. uPA inhibition blocks CSE-induced EMT by reversing E-cadherin and a-catenin expression and retarding the induction of N-cadherin and vimentin, resulting in reduction in migration. uPA overexpression in HSAEpiC cells also promotes EMT and migration. EMT is partly reversed in uPA-overexpressing HSAEpiC cells through the silencing expression of uPA receptor. In conclusion, this study provides new insights into the contribution of uPA upregulation to EMT associated with small airway remodeling in COPD.

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Sputum Cathelicidin, Urokinase Plasminogen Activation System Components, and Cytokines Discriminate Cystic Fibrosis, COPD, and Asthma Inflammation

Cited by 133 publications

References 56 publications

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

Aspergillus fumigatus Generates an Enhanced Th2-Biased Immune Response in Mice with Defective Cystic Fibrosis Transmembrane Conductance Regulator

Involvement of urokinase in cigarette smoke extract-induced epithelial–mesenchymal transition in human small airway epithelial cells

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