Comparison of pro- and anti-inflammatory responses in paired human primary airway epithelial cells and alveolar macrophages.

Autor: Mubarak RA; Department of Medicine, National Jewish Health, 1400 Jackson Street, Room A639, Denver, CO, 80206, USA., Roberts N; Department of Medicine, National Jewish Health, 1400 Jackson Street, Room A639, Denver, CO, 80206, USA., Mason RJ; Department of Medicine, National Jewish Health, 1400 Jackson Street, Room A639, Denver, CO, 80206, USA., Alper S; Department of Biomedical Research and Center for Genes, Environment, and Health, National Jewish Health, University of Colorado, 1400 Jackson Street, Denver, CO, 80206, USA. alpers@njhealth.org.; Department of Immunology and Microbiology, University of Colorado, 1400 Jackson Street, Denver, CO, 80206, USA. alpers@njhealth.org., Chu HW; Department of Medicine, National Jewish Health, 1400 Jackson Street, Room A639, Denver, CO, 80206, USA. chuhw@njhealth.org.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2018 Jun 25; Vol. 19 (1), pp. 126. Date of Electronic Publication: 2018 Jun 25.
DOI: 10.1186/s12931-018-0825-9
Abstrakt: Background: Airway epithelial cells and alveolar macrophages (AMs) are the first line of defense in the lung during infection. Toll-like receptor (TLR) agonists have been extensively used to define the regulation of inflammation in these cells. However, previous studies were performed in non-paired airway epithelial cells and AMs. The major goal of our study was to compare the pro- and anti-inflammatory responses of paired human primary airway epithelial cells and AMs to TLR3 and TLR4 agonists.
Methods: Tracheobronchial epithelial cells (TBEC) and AMs from four smokers and four non-smokers without lung disease were cultured with or without Poly(I:C) (PIC) (a TLR3 agonist) or LPS (a TLR4 agonist) for 4, 24 and 48 h. The immune responses of paired cells were compared.
Results: TBEC and AMs showed stronger pro-inflammatory cytokine (e.g., IL-8) responses to PIC and LPS, respectively. TLR3 and TLR4 mRNA levels were similar in non-stimulated TBEC and AMs. However, PIC stimulation in AMs led to sustained up-regulation of the immune negative regulators Tollip and A20, which may render AMs less sensitive to PIC stimulation than TBEC. Unlike AMs, TBEC did not increase NF-κB activation after LPS stimulation. Interestingly, smoking status was correlated with less TLR3 and IRAK-M expression in non-stimulated TBEC, but not in AMs. PIC-stimulated TBEC and LPS-stimulated AMs from smokers vs. non-smokers produced more IL-8. Finally, we show that expression of A20 and IRAK-M is strongly correlated in the two paired cell types.
Conclusions: By using paired airway epithelial cells and AMs, this study reveals how these two critical types of lung cells respond to viral and bacterial pathogen associated molecular patterns, and provides rationale for modulating immune negative regulators to prevent excessive lung inflammation during respiratory infection.
Databáze: MEDLINE
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