YKL-40 expression in chronic obstructive pulmonary disease: relation to acute exacerbations and airway remodeling

Abstract

BackgroundRecent studies suggest that YKL-40, also called chitinase-3-like-1 protein, has been implicated in the pathogenesis of various inflammatory diseases. It is currently unknown, however, whether YKL-40 plays a role in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and airway remodeling.MethodsWe evaluated serum YKL-40 levels in patients with AECOPD (n = 37) and stable COPD (n = 44), as well as in controls (n = 47). The association between YKL-40 expression and airway remodeling was analyzed. The effects of YKL-40 on collagen synthesis of primary human lung fibroblasts were also evaluated.ResultsSerum YKL-40 levels were elevated at AECOPD onset as compared to stable disease (median [interquartile range], 78.6 [52.3–122.2] ng/ml versus 46.7 [31.2–75.5] ng/ml; p = 0.0005). The ideal cutoff point for distinguishing patients with AECOPD from those with stable COPD was 64.7 ng/ml (AUC: 0.71; 95%CI: 0.596 to 0.823). YKL-40 expression correlated with airflow obstruction, C-reactive protein, and collagen deposition. Stimulation with YKL-40 promoted collagen production in lung fibroblasts through ERK- and p38-dependent mechanisms.ConclusionsYKL-40 expression is up-regulated in patients with COPD and correlates with exacerbation attacks and may contribute to airway remodeling by acting on lung fibroblasts. The current data may provide insight into the underlying pathogenesis of COPD, in which YKL-40 has an important pathogenic role.Trial registrationChiCTR-OCC-13003567Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0338-3) contains supplementary material, which is available to authorized users.

<p>Chitinases and Chitinase-Like Proteins in Obstructive Lung Diseases – Current Concepts and Potential Applications</p>

“…27,61,62,94,95 It has been postulated that it could be related to higher macrophage and neutrophil CHIT1 and YKL-40 expression in COPD patients. 27,36,96 Recent studies showed that the release of CHIT1 is stimulated by interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), lipopolysaccharide (LPS) as well as toll-like receptor (TLR) and nucleotidebinding oligomerization domain (NOD)-2 activation. [97][98][99] The exposure of alveolar macrophages from smokers with and without COPD to CHIT1 resulted in the production of IL-8, MMP-9 and MCP-1, cytokines said to be involved in tissue inflammation, alveolar destruction, and fibrosis.…”

“…Allergen and/or cigarette smoke (CS) exposure have been shown to trigger YKL-40 expression in several cell types (especially neutrophils, macrophages and epithelial cells). 69,92,93,95,96 The induction of YKL-40 expression and secretion may be mediated by various mediators, including interleukin (IL)-1,-13,-17A,-18 and TNFα. 65,69,95,[104][105][106] YKL-40 induces the production of proinflammatory and profibrotic mediators, ultimately resulting in tissue inflammation, alveolar destruction and remodeling.…”

“…These include: 1) the activation and accumulation of dendritic cells (DC), 69 2) significant increase of IL-8 production from bronchial epithelial cells (dependent on MAPK and NF-κB pathway activation), 82 3) prevention of macrophage apoptosis and induction of alternative (M2) macrophage differentiation 69 with enhanced production of cytokines and chemokines, eg, IL-8, TGFβ, MCP-1, MIP-1α and MMP-9, 92 4) increased collagen production from lung fibroblasts (dependent on ERK and p-38 pathway activation). 96 Other inflammatory pathways may also play a role in modulation and aggravation of the YKL-40 response, eg, stimulation of TGFβ production and its activation by IL-13, 103 as well as IL-8 mediated proliferation and migration of bronchial smooth muscle cells. 82 The effects of YKL-40 on pulmonary structure and function are summarized in Figure 3.…”

Protein és glikán biomarkerek szerepe a krónikus obstruktív tüdőbetegség diagnosztikájában

“…Ugyanezt észlelték tüdőszövetben immunhisztokémiával történő kvantitatív mérés során. Eredményeik megerősítik, hogy az YKL40 protein fontos szerepet játszhat a COPD patogenezisében, a légúti gyulladásban és a remodellingben, így alkalmas COPD-biomarker lehet [20].…”

CorelaŢie între chitinase-3-like protein 1 Şi bolile pulmonare cronice

“…Concluziile acestui studiu au fost: creşterea nivelului seric de YKL-40 al pacienţilor cu exacerbare acută a BPOC -s-a demonstat că nivelul seric al YKL-40 la pacienţii fumători cu BPOC a fost mai mare decât la fumătorii care nu aveau BPOC (12,30).…”