Regulation of Proinflammatory Cytokines in Human Lung Epithelial Cells Infected withMycoplasma pneumoniae

Abstract

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␤ mRNA also increased after infection and IL-1␤ 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 cytadherence 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.

Inhibition of message for FcεRI α chain blocks mast cell IL-4 production induced by co-culture with Mycoplasma pneumoniae

“…Peripheral blood mononuclear cells incubated with the organism released IL-2, TNFα, and IL-6 [33][34]. M. pneumoniae co-culture induced IL-8 and IL-1 production by human lung epithelial and monocytoid tumor lines [35][36]. The effects of M. pneumoniae in the activation of diverse cell types is compatible with a model in which the nonspecific aggregation of surface molecules during adherence to at least some cell types results in activation through different cell surface receptors.…”

Mycoplasma pneumoniae as an Under- Recognized Agent of Vasculitic Disorders

“…Interleulin-8 is an inflammatory cytokine and functions as an activator of neutrophils. Several lines of recent in-vitro evidence have supported the pathogenic importance of interleukin-8 in the development of the clinical picture of M. pneumoniae respiratory infection [Chmura et al, 2008;Sohn et al, 2005;Yang et al, 2002]. From this perspective, the activation of interleukin-8 by M. pneumoniae is one of the key steps in inducing the vasculitic disorders which are the main subject of this chapter.…”

Function and Regulation of SPLUNC1 Protein in Mycoplasma Infection and Allergic Inflammation

“…IL-8 has been shown to be an important mediator in host innate immunity, and previous studies have demonstrated the induction of IL-8 by Mp in cultured lung epithelial cells (26). Fig.…”