title: Modulation of IL-8 boosted by Mycoplasma pneumoniae lysate in human airway epithelial cells.
abstract: Mycoplasma pneumoniae, a major cause of community-acquired pneumonia, has been recognized as a trigger for asthma inception and exacerbation. The epithelial cells on the respiratory tract parasitized by M. pneumoniae exhibit a number of cytopathic effects as a result of local inflammation and stimulated host immune response. We investigated the interactions of signaling molecules regulating the release of IL-8 by the direct stimulation of M. pneumoniae lysate (MPL) in human airway epithelial cells. In human airway epithelial cells, MPL-induced IL-8 proteins were decreased by monoclonal anti-TLR2 antibody in a dose-dependent fashion, and significantly blocked by siRNA TLR2. The pharmacologic inhibitors of ERK, U0126 and PD98059, effectively reduced IL-8 expression and the active forms of ERK signaling molecules, as detected by anti-phosphorylated p44/42 antibody. The region spanning from -132 to +41 in the IL-8 promoter demonstrated the highest luciferase activity against MPL and the mutations of NF-κB and NF-IL6 entirely diminished the activity. After investigating transfections of the NF-κB and NF-IL6 reporter vectors, NF-IL6 activation was significantly induced by MPL stimulation, which was considerably decreased by U0126 and monoclonal anti-TLR2 antibody. These results indicate that MPL-induced IL-8 increase is transcriptionally regulated by NF-IL6 more than by NF-κB. Additionally, the activation of NF-IL6 is influenced by TLR2 and ERK signaling pathways in airway epithelial cells.
authors.affiliation: Department of Pediatrics and Institute of Allergy, BioMedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Hong
authors.forename: Kyu Earn
authors.initials: KE
authors.lastname: Kim
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Sohn
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology; D002070:Butadienes / Q000494:pharmacology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D020935:MAP Kinase Signaling System; D009177:Mycoplasma pneumoniae / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
chemical_list: D019138:Antibodies, Blocking; D000942:Antigens, Bacterial; D002070:Butadienes; D022782:CCAAT-Enhancer-Binding Protein-beta; D005419:Flavonoids; D016209:Interleukin-8; D016328:NF-kappa B; D009570:Nitriles; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C113580:U 0126; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one