Gene expression of Toll-like receptors and associated molecules induced by inflammatory stimuli in the primary alveolar macrophage.
We investigated the expression of Toll-like receptors (TLRs) and associated signaling molecules in inflammatory stimuli-activated murine primary alveolar macrophage (AM) in vitro, and in a murine model of acute lung injury. The results demonstrated three patterns of gene expression: the TLR2 and myeloid differentiation factor 88 (MyD88) gene expressions were induced in AM in response to lipopolysaccharide (LPS), interleukin (IL)-1beta, or tumor necrosis factor-alpha or in the lung tissue of an LPS-induced acute lung injury model; the gene expressions of TLR1, -3, -6, CD14, and MD2 were unchanged; and the TLR4 and TLR5 gene expressions were downregulated in AM following inflammatory stimuli. Furthermore, the LPS-induced upregulation of the TLR2 gene was mediated via the activation of NF-kappaB. These results indicate that the TLR2 expression upregulated in AM following bacterial respiratory infections may render AM responsive to TLR2 ligands, which may enhance innate immunity against pathogens in the lung.
Oshikawa
Katsuhisa
K
Division of Pulmonary Medicine, Department of Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan. oshikatu@jichi.ac.jp
Sugiyama
Yukihiko
Y
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008171:Lung Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D003513:Cycloheximide