Abstract
The role of inflammation in airway epithelial cells and its regulation are important in several respiratory diseases. When disease is present, the barrier between the pulmonary circulation and the airway epithelium is damaged, allowing serum proteins to enter the airways. We identified that human glycated albumin (GA) is a molecule in human serum that triggers an inflammatory response in human airway epithelial cultures. We observed that single-donor human serum induced IL-8 secretion from primary human airway epithelial cells and from a cystic fibrosis airway cell line (CF1-16) in a dose-dependent manner. IL-8 secretion from airway epithelial cells was time dependent and rapidly increased in the first 4 h of incubation. Stimulation with GA promoted epithelial cells to secrete IL-8, and this increase was blocked by the anti-GA antibody. The IL-8 secretion induced by serum GA was 10–50-fold more potent than TNFα or LPS stimulation. GA also has a functional effect on airway epithelial cells in vitro, increasing ciliary beat frequency. Our results demonstrate that the serum molecule GA is pro-inflammatory and triggers host defense responses including increases in IL-8 secretion and ciliary beat frequency in the human airway epithelium. Although the binding site of GA has not yet been described, it is possible that GA could bind to the receptor for advanced glycated end products (RAGE), known to be expressed in the airway epithelium; however, further experiments are needed to identify the mechanism involved. We highlight a possible role for GA in airway inflammation.
Highlights
Airway epithelial cells participate in host defense by generating a wide variety of cytokines and chemokines that initiate or amplify acute and chronic inflammation by mediating the recruitment, activation, and survival of inflammatory cells within the airway (Standiford et al, 1990; Marini et al, 1992; Levine, 1995)
Interleukin 8 (IL-8) is a pro-inflammatory molecule that is found in high concentration in the bronchial alveolar lavage (BAL) of patients with airway inflammatory diseases like cystic fibrosis (CF) (Konstan et al, 1994; O’Sullivan and Fredman, 2009), asthma (Lamblin et al, 1998), and chronic obstructive pulmonary disease (COPD) (Keatings et al, 1996; Hollander et al, 2007) and in the nasal mucosa of patients with allergic rhinitis (Cui et al, 2015)
The results demonstrated that the unknown protein (UP) and GA had a strong signal while human albumin (HA) had a very small response as expected, as the monoclonal antibody used targeted GA and may not react with non-glycated albumin
Summary
Airway epithelial cells participate in host defense by generating a wide variety of cytokines and chemokines that initiate or amplify acute and chronic inflammation by mediating the recruitment, activation, and survival of inflammatory cells within the airway (Standiford et al, 1990; Marini et al, 1992; Levine, 1995). IL-8 is thought to play a major regulatory role in the airways as a potent chemo-attractant of polymorphonuclear granulocytes (PMNs) (Nakamura et al, 1991). In airway diseases such as CF, asthma, and respiratory infections including viral infections notably SARS-CoV-2, the epithelial barrier is injured causing increased permeability and markedly greater plasma and serum protein movement across this barrier (McElvaney et al, 1992), a possible mechanism leading to a worse outcome in COVID-19 patients. The efficiency of MCC is affected by airway inflammation, which in turn induces the release of local pro-inflammatory molecules resulting in mucus hypersecretion or ciliary dysfunction (Seybold et al, 1990; Cowley et al, 1997; Waugh and Wilson, 2008; Schmid et al, 2010; Koblizek et al, 2011)
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