CpG DNA-mediated immune response in pulmonary endothelial cells.
Although the CpG DNA immune response mediated by Toll-like receptor 9 (TLR9) has been extensively studied in a number of immune cells, the response to CpG DNA in endothelial cells (EC) is not well understood. In this study, we show that both mouse and rat lung EC display constitutive expression of TLR9 mRNA. Exposure to CpG DNA induced a potent proinflammatory response as manifested by an increased expression of IL-8 and ICAM-1 in mouse pulmonary EC. The proinflammatory response was sensitive to chloroquine, consistent with a role of endosomal contribution. A role for p38 MAPK and NF-kappaB pathway was apparent as the response was sensitive to inhibitors of p38 MAPK and NF-kappaB but was not affected by inhibitors of ERK1/2. A synergistic effect of CpG DNA and LPS on the inflammatory response is consistent with multiple TLR interaction in EC. This study suggests a possible role for CpG DNA-mediated EC immune response in the host defense system. It also has important implications in plasmid DNA-mediated pulmonary endothelium gene transfer.
Li
Jiang
J
Center for Pharmacogenetics, Univ. of Pittsburgh, School of Pharmacy, 639 Salk Hall, Pittsburgh, PA 15261, USA.
Ma
Zheng
Z
Tang
Zhi-Lue
ZL
Stevens
Troy
T
Pitt
Bruce
B
Li
Song
S
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D018899:CpG Islands / Q000276:immunology*; D004269:DNA, Bacterial / Q000276:immunology / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D004357:Drug Synergism; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D018014:Gene Transfer Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009841:Oligonucleotides / Q000276:immunology / Q000494:pharmacology*; D010957:Plasmids / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9; D015854:Up-Regulation / Q000276:immunology
D000962:Antimalarials; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009841:Oligonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D018799:Intercellular Adhesion Molecule-1; D002738:Chloroquine