Induction of IL-8 byMycoplasma pneumoniaemembrane in BEAS-2B cells

Abstract

Mycoplasma pne umoniae 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-κB 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-α-induction of IL-8, each failed to inhibit MMF-induction of IL-8.

Pulmonary Surfactant Phosphatidylglycerol Inhibits Mycoplasma pneumoniae-stimulated Eicosanoid Production from Human and Mouse Macrophages

“…Previous reports showed that live M. pneumoniae infection induces IL-8 expression from human lung epithelial cells and macrophages. Additionally, our recent study showed that M. pneumoniae membrane and LPP induced IL-8 production from BEAS-2B cells and that NF-B and to a lesser extent the MAPK pathways played an important role in the induction (14).…”

“…Although M. pneumoniae is a well established cause of asthma exacerbations, more recent data have suggested that it may also contribute to the pathogenesis of asthma (7)(8)(9)(10)(11)(12). The lipoprotein constituents of M. pneumoniae membrane play a critical role in immune recognition by the host and induction of the inflammatory response (13,14). The membrane components are recognized mainly by the Toll-like receptors, TLR1, 2 TLR2, and TLR6, that initiate downstream signaling events including activation of NF-B and the mitogen-activated protein kinases (MAPKs) (15).…”

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.…”

Macrolide-resistant Mycoplasma pneumoniae: characteristics of isolates and clinical aspects of community-acquired pneumonia

“…Several membrane proteins in M. pneumoniae have high affinity for various surface receptors on host cells [77]. Through interaction with recognition receptors, including toll-like receptors 2 and 6, mycoplasma membrane lipoproteins are able to induce host immune responses [77,78]. Adherence of M. pneumoniae to host cells in the respiratory tract is mediated by the P1 adhesin protein and accessory proteins [79][80][81][82].…”

“…ML possess antimicrobial activity against M. pneumoniae, and also have anti-inflammatory effects. For example, CAM is able to suppress IL-8 induction, even in ML r M. pneumoniae infection [78,86,90]. Thus, clinical efficacy of ML in treating M. pneumoniae infection may reflect not only direct antimicrobial activity but also anti-inflammatory effects of inhibition of production of cytokines, including IL-8.…”