Differences in LPS-induced activation of bronchial epithelial cells (BEAS-2B) and type II-like pneumocytes (A-549).
Lipopolysaccharide (LPS) as a major component of the outer membrane of gram-negative bacteria stimulates various cells to initiate a signalling cascade which ultimately leads to cell activation and expression of immunoregulatory or inflammatory cytokines. The human respiratory epithelium is an important environmental interface, but differences in LPS-induced cell activation between bronchial and alveolar epithelial cells have not yet been investigated in detail. First, the expression of Toll-like receptors (TLRs), as pattern-recognition receptors, was investigated for the bronchial epithelial cells and type II-like pneumocytes, demonstrating that they fulfil the prerequisites for LPS signalling. Thereafter, the effects of LPS, soluble CD14 (sCD14) and LPS-binding protein (LBP) on the release of interleukin-6 (IL-6) and IL-8 were studied. In the presence of LPS, sCD14 induced a significant and concentration-dependent cytokine release in type II-like pneumocytes, whereas the response of bronchial epithelial cells to sCD14 stimulation was low, implicating sCD14-independent activation mechanisms. Furthermore, LBP revealed inhibitory effects on the activation of alveolar epithelial cells, which may represent a novel local defence mechanism during gram-negative infection. We conclude that distinct pathways exist for LPS-induced activation of bronchial and alveolar epithelial cells.
Schulz
C
C
Medizinische Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Germany. christian.schulz@klinik.uni-regensburg.de
Farkas
L
L
Wolf
K
K
Kratzel
K
K
Eissner
G
G
Pfeifer
M
M
D000209:Acute-Phase Proteins; D000906:Antibodies / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002352:Carrier Proteins / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology*; D051193:Toll-Like Receptors; D014407:Tumor Cells, Cultured; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000906:Antibodies; D002352:Carrier Proteins; D029721:Drosophila Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein