Researchers at Lund University in Sweden recently revealed an interaction between specific protein factors and hypoxia conditions associated with two lung disorders, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). The study was published in the journal BMC Pulmonary Medicine and is entitled “Hypoxia down-regulates expression of secretory leukocyte protease inhibitor in bronchial epithelial cells via TGF-β1.”
The secretory leukocyte protease inhibitor (SLPI) corresponds to a small protein that is secreted by the airway epithelium. It has anti-protease properties that are important to neutralize specific enzymes and prevent excessive damage to tissues during inflammation. SLPI has antimicrobial properties as well. It is thought that the balance between proteases, anti-proteases and innate defense mechanisms play a determinant role in inflammatory lung diseases, such as COPD and CF.
COPD is a progressive disease in which individuals develop serious breathing-related problems due to obstruction of the airways, such as wheezing, shortness of breath, chest tightness and acute exacerbations. CF is a life-threatening genetic disease in which a defective gene causes the body to form unusually thick, sticky mucus that is difficult to cough up and can result in serious respiratory and gastrointestinal manifestations. Both lung diseases have a high protease burden in the airways that result in tissue damage, and an impaired innate immunity that leads to bacterial colonization and frequent airway infections. Both inflammation and infection cause deterioration of the respiratory function and lead to a hypoxic microenvironment with low oxygen levels.
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In this study, the impact of hypoxia in SLPI secretion by the respiratory epithelium was assessed. Researchers used primary human bronchial epithelial cells and analyzed the release of SLPI in normal oxygen conditions (21% oxygen) and in hypoxia (1% oxygen). The expression of transforming growth factor beta-1 (TGF-β1) was also assessed, as it has been implicated in several inflammatory pulmonary conditions and has also been shown to regulate SLPI expression.
Researchers found that in response to hypoxia, SLPI expression is decreased in bronchial epithelial cells, while the expression of TGF-β1 is increased. Furthermore, bronchial epithelial cells in normal oxygen conditions that were exposed to TGF-β1 also experienced a reduction in SLPI production, showing that this reduction is mediated by TGF-β1. Neutralizing antibodies against TGF-β1 were able to partially restore SLPI expression in hypoxia conditions.
The research team concluded that hypoxia, which is associated with several lung diseases, leads to a decrease in SLPI expression in the airway epithelium and may explain the protease/anti-protease imbalance observed in these medical conditions. The researchers believe that SLPI may also be a potential therapeutic target for the treatment and prevention of exacerbations in patients with inflammatory lung diseases.