Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

Schmeck, Bernd; Moog, Kerstin; Zahlten, Janine; Laak, Vincent van; N′Guessan, Philippe Dje; Opitz, Bastian; Rosseau, Simone; Suttorp, Norbert; Hippenstiel, Stefan

doi:10.1186/1465-9921-7-98

Cited by 60 publications

(47 citation statements)

References 44 publications

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“…But NF-B does not appear to be the only driver of IL-8 expression induced by L. pneumophila. Another important player could be AP-1 because it is known to participate in IL-8 gene regulation in general (37) and in bacterial infections in particular (9).…”

Section: Discussionmentioning

confidence: 99%

“…However, although Legionella bacteria replicate efficiently within lung epithelial cells (3,4) and recent studies pointed to the lung epithelium as an important sentinel and effector system of innate immunity (5)(6)(7)(8), little is known about the consequences of pulmonary epithelial cell infection with L. pneumophila. Upon infection, activated lung epithelium may contribute to the regulation of the immune response by the liberation of numerous proinflammatory mediators (9,10). As an example, liberation of the CXC chemokine IL-8 plays an important role for the recruitment of immune cells, like macrophages and granulocytes, to the site of infection in the lung (11).…”

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confidence: 99%

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Histone Acetylation and Flagellin Are Essential for Legionella pneumophila-Induced Cytokine Expression

Schmeck

Lorenz

N′Guessan

et al. 2008

The Journal of Immunology

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Legionella pneumophila causes severe pneumonia. Acetylation of histones is thought to be an important regulator of gene transcription, but its impact on L. pneumophila-induced expression of proinflammatory cytokines is unknown. L. pneumophila strain 130b induced the expression of the important chemoattractant IL-8 and genome-wide histone modifications in human lung epithelial A549 cells. We analyzed the IL-8-promoter and found that histone H4 was acetylated and H3 was phosphorylated at Ser10 and acetylated at Lys14, followed by transcription factor NF-κB. Recruitment of RNA polymerase II to the IL-8 promoter corresponded with increases in gene transcription. Histone modification and IL-8 release were dependent on p38 kinase and NF-κB pathways. Legionella-induced IL-8 expression was decreased by histone acetylase (HAT) inhibitor anacardic acid and enhanced by histone deacetylase (HDAC) inhibitor trichostatin A. After Legionella infection, HATs p300 and CREB-binding protein were time-dependently recruited to the IL-8 promoter, whereas HDAC1 and HDAC5 first decreased and later reappeared at the promoter. Legionella specifically induced expression of HDAC5 but not of other HDACs in lung epithelial cells, but knockdown of HDAC1 or 5 did not alter IL-8 release. Furthermore, Legionella-induced cytokine release, promoter-specific histone modifications, and RNA polymerase II recruitment were reduced in infection with flagellin-deletion mutants. Legionella-induced histone modification as well as HAT-/HDAC-dependent IL-8 release could also be shown in primary lung epithelial cells. In summary, histone acetylation seems to be important for the regulation of proinflammatory gene expression in L. pneumophila infected lung epithelial cells. These pathways may contribute to the host response in Legionnaires’ disease.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Histone Acetylation and Flagellin Are Essential for Legionella pneumophila-Induced Cytokine Expression

Schmeck

Lorenz

N′Guessan

et al. 2008

The Journal of Immunology

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“…This transcription factor, along with c-Fos, FosB, FOSL1/2, JunB, JunD and c-MAF, are members of the AP-1 family of transcription factors [54]. Once activated by phosphorylation they can form hetero-or homodimers, and can induce the transcription of many genes including cytokines, which has been shown for several different tissues, for example lung epithelial cells and mast cells, to produce TNF-a and ILs, which are potent mediators of various inflammatory conditions including IBD [55][56][57].…”

Section: The Jnk Mapkmentioning

confidence: 99%

Mitogen activated protein kinases: a role in inflammatory bowel disease?

Broom

Widjaya

Troelsen

et al. 2009

Clinical and Experimental Immunology

160

114

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SummarySince their discovery more than 15 years ago, the mitogen activated protein kinases (MAPK) have been implicated in an ever-increasingly diverse array of pathways, including inflammatory signalling cascades. Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are characterized by the perpetual production of inflammatory mediators. Research into the transduction pathway behind this over-production has highlighted the potential mediating role for the MAPKs and their related signalling components. This review highlights some of the research into the role for the MAPKs and their related signalling proteins in influencing the progression of IBD.

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“…Bioplex protein array system Confluent A549 cells were infected as indicated in a humidified atmosphere for 15 h. After incubation, supernatants were collected and cytokine release was analysed using the Bioplex Protein Array system (BioRad, Hercules, CA, USA) and beads specific for IL-2, -4, -5, -6, -7, -8, -10, -12 (p70), -13 and -17, MCP-1, TNF-a, IL-1b, IFN-c, granulocyte-macrophage colonystimulating factor (GM-CSF) and G-CSF, according to the manufacturer's instructions [19,20].…”

Section: Cell Linesmentioning

confidence: 99%

Legionella pneumophila-induced NF-κB- and MAPK-dependent cytokine release by lung epithelial cells

Schmeck¹,

N′Guessan²,

Ollomang³

et al. 2006

Eur Respir J

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Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with the alveolar epithelium. The aim of this study was to investigate whether L. pneumophila infection of lung epithelial cells (A549) resulted in proinflammatory activation.L. pneumophila infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte chemoattractant protein-1, tumour necrosis factor-a, IL-1b, interferon-c and granulocyte colonystimulating factor, but not of IL-5, -7, -10, -12 (p70) or -13 or granulocyte-macrophage colonystimulating factor. The present study focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 mitogen-activated protein kinase (MAPK) was activated and kinase inhibition reduced secretion of induced cytokines, with the exception of IL-2 and granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase 1/ extracellular signal-regulated kinase pathway only reduced the expression of a few cytokines. L. pneumophila also induced binding of nuclear factor-kB subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific inhibitor of the inhibitor of nuclear factor-kB complex dosedependently lowered IL-8 expression.Taken together, Legionella pneumophila activated p38 mitogen-activated protein kinase-and nuclear factor-kB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to the immune response in legionellosis.

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Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

Cited by 60 publications

References 44 publications

Histone Acetylation and Flagellin Are Essential for Legionella pneumophila-Induced Cytokine Expression

Histone Acetylation and Flagellin Are Essential for Legionella pneumophila-Induced Cytokine Expression

Mitogen activated protein kinases: a role in inflammatory bowel disease?

Legionella pneumophila-induced NF-κB- and MAPK-dependent cytokine release by lung epithelial cells

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