Regulation of toll-like receptor 2 and 4 gene expression in murine alveolar macrophages.
The authors investigated the regulation of toll-like receptor (TLR) TLR2 and TLR4 gene expression in alveolar macrophage (AM) in response to lipopolysaccharide (LPS) or proinflammatory cytokines in vitro. Treatment of a murine AM cell line, MH-S, with LPS, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta significantly increased TLR2 mRNA expression, whereas TLR4 mRNA expression remained constant. LPS-mediated TLR2 mRNA up-regulation was attenuated by inhibition of p38 kinase (with SB203580) or nuclear factor (NF)-kappaB (with sulfasalazine or SN-50), but not by inhibition of extracellular signal-regulated kinase (with PD98059) or c-Jun N-terminal kinase (with SP600125), suggesting that LPS may induce TLR2 mRNA expression through p38 kinase and NF-kappaB activation. These results indicate that TLR2 expression up-regulated in AM in response to bacterial respiratory infections may render AM responsive to TLR2 ligands, which may accelerate the 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
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000276:immunology* / Q000633:toxicity; D020935:MAP Kinase Signaling System; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012460:Sulfasalazine / Q000494:pharmacology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation
D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010455:Peptides; D011956:Receptors, Cell Surface; C118258:SN50 peptide; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D012460:Sulfasalazine; D020928:Mitogen-Activated Protein Kinases