Induction of IL-8 by Mycoplasma pneumoniae membrane in BEAS-2B cells.
Mycoplasma pneumoniae is an extracellular pathogen, residing on mucosal surfaces of the respiratory and genital tracts. The lack of cell walls in mycoplasmas facilitates the direct contact of the bacterial membrane with the host cell. The cell membrane of mycoplasma is the major inducer of the host pathogenic response. Airway diseases caused by M. pneumoniae include bronchiolitis, bronchitis, and rarely bronchiectasis. In such disorders, neutrophil infiltration of the airways predominates. More recently, M. pneumoniae has been implicated in the pathogenesis of asthma. Epithelial cells play an important role in recruiting inflammatory cells into the airways. Since M. pneumoniae infection of human epithelial cells induces expression of IL-8-a potent activator of neutrophils-we investigated the signaling and transcriptional mechanisms by which mycoplasma membrane induces expression of this chemokine. In BEAS-2B human bronchial epithelial cells, mycoplasma membrane fraction (MMF) increased IL-8 mRNA and protein production. Activation of the transcriptional elements activating protein-1, nuclear factor-interleukin-6, and particularly NF-kappaB are essential for optimal IL-8 production by MMF. The mitogen-activated protein kinases individually played a modest role in MMF-induced IL-8 production. Toll-like receptor-2 did not play a significant role in MMF-induction of IL-8. Antibiotics with microbicidal activity against M. pneumoniae are also known to have anti-inflammatory effects. Whereas clarithromycin, azithromycin, and moxifloxacin individually were able to inhibit TNF-alpha-induction of IL-8, each failed to inhibit MMF-induction of IL-8.
Chmura
Kathryn
K
Department of Medicin, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Bai
Xiyuan
X
Nakamura
Mari
M
Kandasamy
Pitchaimani
P
McGibney
Mischa
M
Kuronuma
Koji
K
Mitsuzawa
Hiroki
H
Voelker
Dennis R
DR
Chan
Edward D
ED
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D001980:Bronchi / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D009177:Mycoplasma pneumoniae; D011019:Pneumonia, Mycoplasma / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000900:Anti-Bacterial Agents; C508606:CXCL8 protein, human; D016209:Interleukin-8; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases