IL-8 and IP-10 expression from human bronchial epithelial cells BEAS-2B are promoted by Streptococcus pneumoniae endopeptidase O (PepO)

• Published in: BMC microbiology Vol. 17; no. 1; p. 187
• Main Authors: Zou, Jiaqiong, Zhou, Long, Hu, Chunlan, Jing, Peng, Guo, Xiaolan, Liu, Sulan, Lei, Yan, Yang, Shangyu, Deng, Jiankang, Zhang, Hong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.08.2017; BioMed Central; BMC
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Bacterial Proteins - administration & dosage; Bacterial Proteins - pharmacology; BEAS-2B; Bronchi - metabolism; Cell culture; Cell Line; Chemokine CXCL10 - genetics; Chemokine CXCL10 - metabolism; Chemokines; Chromatography; Cytokines; Cytokines - metabolism; Dendritic cells; eIF-2 Kinase - drug effects; Endopeptidases; Enzymes; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium; Gene expression; Gene Expression Regulation, Enzymologic; Genetic aspects; Health aspects; Humans; Il-8; Inflammation; Inhibitors; Interferon; Interleukin 8; Interleukin-8 - genetics; Interleukin-8 - metabolism; Interleukins; IP-10; IP-10 protein; Kinases; Ligands; Lymphocytes; MAP kinase; Metalloendopeptidases - administration & dosage; Metalloendopeptidases - pharmacology; Mitogen-Activated Protein Kinase Kinases - drug effects; Neutrophils; NF-KappaB Inhibitor alpha - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Pathogenesis; Pathogens; PepO; Peptidoglycans; Pharmacology; Phosphatidylinositol 3-Kinases; Phosphorylation; Pneumolysin; Pneumonia; Polysaccharides; Protein A; Proteins; PspA protein; Recombinant Proteins - metabolism; Recruitment; Saccharides; Signal Transduction - drug effects; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - metabolism; Streptococcus pneumoniae - pathogenicity; Studies; Surface protein A; Time Factors; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Transcription, Genetic; Virulence; Virulence Factors; PepO; BEAS-2B; IP-10; Il-8
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/s12866-017-1081-8

The bronchial epithelium serves as the first defendant line of host against respiratory inhaled pathogens, mainly through releasing chemokines (e.g. interleukin-8 (IL-8), interferon-induced protein 10 (IP-10) etc.) responsible for neutrophil or lymphocyte recruitment to promote the clearance of inhaled pathogens including Streptococcus pneumoniae (S. pneumoniae). Previous studies have shown that IL-8 expression is induced by pneumococcal virulence factors (e.g. pneumolysin, peptidoglycan-polysaccharides, pneumococcal surface protein A (PspA) etc.), which contributes to the pathogenesis of pneumonia. Whether other pneumococcal virulence factors are involved in inducing chemokines expression in epithelium is still unknown. We studied the effect of PepO, a widely expressed and newly discovered pneumococcal virulence protein, on the release of proinflammatory cytokines, IL-8 and IP-10, from human bronchial epithelial cell line BEAS-2B and identified the relevant signaling pathways. Incubation of BEAS-2B with PepO resulted in increased synthesis and release of IL-8 and IP-10 in a dose and time independent manner. We also detected the increased and sustained expression of TLR2 and TLR4 transcripts in BEAS-2B stimulated by PepO. PepO activation leaded to the phosphorylation of MAPKs, Akt and p65. Pharmacologic inhibitors of MAPKs, PI3K and IκB-α phosphorylation attenuated IL-8 release, while IP-10 production was just suppressed by inhibitors of IκB-α phosphorylation, PI3K and P38 MAPK. These results suggest that PepO enhances IL-8 and IP-10 production in BEAS-2B in a MAPKs-PI3K/Akt-p65 dependent manner, which may play critical roles in the pathogenesis of pneumonia.