Abstract
Neutrophilic inflammation results in loss of lung function in chronic obstructive pulmonary disease (COPD). Gram-negative bacteria, such as nontypeable Haemophilus influenzae (NTHi), trigger acute exacerbations of COPD (AECOPD) and contribute to chronic lung inflammation. The pro-inflammatory cytokine interleukin-17C (IL-17C) is expressed by airway epithelial cells and regulates neutrophilic chemotaxis. Here, we explored the function of IL-17C in NTHi- and cigarette smoke (CS)-induced models of COPD. Neutrophilic inflammation and tissue destruction were decreased in lungs of IL-17C-deficient mice (Il-17c-/-) chronically exposed to NTHi. Numbers of pulmonary neutrophils were decreased in Il-17c-/- mice after acute exposure to the combination of NTHi and CS. However, Il-17c-/- mice were not protected from CS-induced lung inflammation. In a preliminary patient study, we show that IL-17C is present in sputum samples obtained during AECOPD and associates with disease severity. Concentrations of IL-17C were significantly increased during advanced COPD (GOLD III/IV) compared to moderate COPD (GOLD I/II). Concentrations of IL-17A and IL-17E did not associate with disease severity. Our data suggest that IL-17C promotes harmful pulmonary inflammation triggered by bacteria in COPD.
Highlights
Cigarette smoke (CS) and exposure to indoor air pollution are the major risk factors for the development of chronic obstructive pulmonary disease (COPD) which is expected to become the fourth leading cause of death worldwide by 2030
We demonstrate that IL-17C is present in sputum of COPD patients during acute exacerbations of COPD (AECOPD) and provide evidence that concentrations of IL-17C associate with disease severity
Morphometry showed that the mean chord length (MCL) values in lungs from nontypeable Haemophilus influenzae (NTHi)-exposed Il-17c-/- mice were significantly decreased compared with NTHi-exposed WT mice indicating that deficiency for IL-17C partially protects loss of lung structure (Fig 2E)
Summary
Cigarette smoke (CS) and exposure to indoor air pollution are the major risk factors for the development of chronic obstructive pulmonary disease (COPD) which is expected to become the fourth leading cause of death worldwide by 2030. COPD is characterized by chronic lung inflammation which associates with increased numbers of pulmonary neutrophils, macrophages, and T lymphocytes [1, 2]. Lungs of COPD patients are frequently infected with Gramnegative bacteria, such as nontypeable Haemophilus influenzae (NTHi), which amplify chronic. University within the funding programme Open Access Publishing
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