Regulation of proinflammatory cytokines in human lung epithelial cells infected with Mycoplasma pneumoniae.
Mycoplasma pneumoniae is a small bacterium without a cell wall that causes tracheobronchitis and atypical pneumonia in humans. It has also been associated with chronic conditions, such as arthritis, and extrapulmonary complications, such as encephalitis. Although the interaction of mycoplasmas with respiratory epithelial cells is a critical early phase of pathogenesis, little is known about the cascade of events initiated by infection of respiratory epithelial cells by mycoplasmas. Previous studies have shown that M. pneumoniae can induce proinflammatory cytokines in several different study systems including cultured murine and human monocytes. In this study, we demonstrate that M. pneumoniae infection also induces proinflammatory cytokine expression in A549 human lung carcinoma cells. Infection of A549 cells resulted in increased levels of interleukin-8 (IL-8) and tumor necrosis factor alpha mRNA, and both proteins were secreted into culture medium. IL-1 beta mRNA also increased after infection and IL-1 beta protein was synthesized, but it remained intracellular. In contrast, levels of IL-6 and gamma interferon mRNA and protein remained unchanged or undetectable. Using protease digestion and antibody blocking methods, we found that M. pneumoniae cytoadherence is important for the induction of cytokines. On the other hand, while M. pneumoniae protein synthesis and DNA synthesis do not appear to be prerequisites for the induction of cytokine gene expression, A549 cellular de novo protein synthesis is responsible for the increased cytokine protein levels. These results suggest a novel role for lung epithelial cells in the pathogenesis of M. pneumoniae infection and provide a better understanding of M. pneumoniae pathology at the cellular level.
Yang
Jun
J
Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. jdy6@cdc.gov
Hooper
W Craig
WC
Phillips
Donald J
DJ
Talkington
Deborah F
DF
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000276:immunology; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000276:immunology; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D008168:Lung / Q000166:cytology; D009177:Mycoplasma pneumoniae / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha