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The primary function of the bronchial epithelium is to act as a defensive barrier aiding the maintenance of normal airway function. Bronchial epithelial cells (BEC) form the interface between the external environment and the internal milieu, making it a major target of inhaled insults. However, BEC can also serve as effectors to initiate and orchestrate immune and inflammatory responses by releasing chemokines and cytokines, which recruit and activate inflammatory cells. They also produce excess reactive oxygen species as a result of an oxidant/antioxidant imbalance that contributes to chronic pulmonary inflammation and lung tissue damage. Accumulated mucus from hyperplastic BEC obstructs the lumen of small airways, whereas impaired cell repair, squamous metaplasia and increased extracellular matrix deposition underlying the epithelium is associated with airway remodelling particularly fibrosis and thickening of the airway wall. These alterations in small airway structure lead to airflow limitation, which is critical in the clinical diagnosis of chronic obstructive pulmonary disease (COPD). In this review, we discuss the abnormal function of BEC within a disturbed immune homeostatic environment consisting of ongoing inflammation, oxidative stress and small airway obstruction. We provide an overview of recent insights into the function of the bronchial epithelium in the pathogenesis of COPD and how this may provide novel therapeutic approaches for a number of chronic lung diseases.

Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Klotho, an anti-aging protein, has an anti-inflammatory function. However, the role of Klotho has never been investigated in COPD. The aim of this study is to investigate the possible role of Klotho by alveolar macrophages in airway inflammation in COPD. Klotho levels were assessed in the lung samples and peripheral blood mononuclear cells of non-smokers, smokers, and patients with COPD. The regulation of Klotho expression by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced inflammation. Klotho expression was reduced in alveolar macrophages in the lungs and peripheral blood mononuclear cells of COPD patients. CSE decreased Klotho expression and release from MH-S cells. Knockdown of endogenous Klotho augmented the expression of the inflammatory mediators, such as MMP-9, IL-6, and TNF-α, by MH-S cells. Exogenous Klotho inhibited the expression of CSE-induced inflammatory mediators. Furthermore, we showed that Klotho interacts with IκBα of the NF-κB pathway. Dexamethasone treatment increased the expression and release level of Klotho in MH-S cells. Our findings suggest that Klotho plays a role in sustained inflammation of the lungs, which in turn may have therapeutic implications in COPD.

The primary function of the bronchial epithelium is to act as a defensive barrier aiding the maintenance of normal airway function. Bronchial epithelial cells (BEC) form the interface between the external environment and the internal milieu, making it a major target of inhaled insults. However, BEC can also serve as effectors to initiate and orchestrate immune and inflammatory responses by releasing chemokines and cytokines, which recruit and activate inflammatory cells. They also produce excess reactive oxygen species as a result of an oxidant/antioxidant imbalance that contributes to chronic pulmonary inflammation and lung tissue damage. Accumulated mucus from hyperplastic BEC obstructs the lumen of small airways, whereas impaired cell repair, squamous metaplasia and increased extracellular matrix deposition underlying the epithelium is associated with airway remodelling particularly fibrosis and thickening of the airway wall. These alterations in small airway structure lead to airflow limitation, which is critical in the clinical diagnosis of chronic obstructive pulmonary disease (COPD). In this review, we discuss the abnormal function of BEC within a disturbed immune homeostatic environment consisting of ongoing inflammation, oxidative stress and small airway obstruction. We provide an overview of recent insights into the function of the bronchial epithelium in the pathogenesis of COPD and how this may provide novel therapeutic approaches for a number of chronic lung diseases.