Molecular Regulation of Granulocyte Macrophage Colony-Stimulating Factor in Human Lung Epithelial Cells by Interleukin (IL)-1 β , IL-4, and IL-13 Involves Both Transcriptional and Post-Transcriptional Mechanisms

Bergmann, Martin; Barnes, Peter J.; Newton, Robert

doi:10.1165/ajrcmb.22.5.3889

Cited by 52 publications

(51 citation statements)

References 44 publications

(44 reference statements)

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“…PKC activation by PMA has been shown to stimulate NF-kB activation and to induce granulocyte-macrophage colonystimulating factor (GM-CSF) expression in A549 cells and human bronchial epithelial cells [40,41]. In addition, several studies have demonstrated airway epithelial cell TNF-a responses to be at least partially sensitive to PKC inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Slevogt

Maqami²,

Vardarowa³

et al. 2008

European Respiratory Journal

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Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. In pulmonary epithelial cells, M. catarrhalis induces release of the proinflammatory cytokine interleukin (IL)-8, which plays a pivotal role in orchestrating airway inflammation.The present study demonstrated that protein kinase (PK)C was activated by Moraxella infection and positively regulated M. catarrhalis-triggered nuclear factor (NF)-kB activation and subsequent IL-8 release. Activation of the PKC/NF-kB signalling pathway was found to be dependent on expression of the Moraxella-specific ubiquitous surface protein A2. In addition, it was shown that specific isoforms of PKC play differential roles in the fine-tuning of the M. catarrhalis-induced NFkB-dependent gene expression through controlling il8 promoter activity. Inhibition of PKCa and e with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCh increased, the M. catarrhalis-induced IL-8 transcription and cytokine release.In conclusion, it was shown that Moraxella catarrhalis infection activates protein kinase C and its isoforms a, e and h, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Slevogt

Maqami²,

Vardarowa³

et al. 2008

European Respiratory Journal

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“…IL-13 increases VCAM1 expression on endothelial cells (34), which enhances eosinophil adherence via ␤ 1 integrin. IL-13 also increases CD69 expression on eosinophils (35) and the production of GM-CSF by epithelial cells (36). Both of these actions increase eosinophil survival.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the 5q31-q33 Locus Shows an Association between IL13-1055C/T IL-13-591A/G Polymorphisms and Schistosoma haematobium Infections

Kouriba

Chevillard

Bream

et al. 2005

The Journal of Immunology

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Millions of humans are exposed to schistosome infections, which cause severe kidney and liver disease and 280,000 deaths annually. Th2-mediated immunity is critical to human defenses against this pathogen and susceptibility to infection is controlled by a major genetic locus that includes IL4, IL5, and IL13 genes. These observations led us to evaluate whether certain polymorphisms in IL4, IL5, or IL13 determine schistosome infection. The study was performed in two Dogon villages where Schistosoma haematobium is endemic. Schistosome infections were evaluated by counting eggs and measuring worm Ags in urine. Genetic polymorphisms were determined by restriction enzyme analysis or by primer extension and denaturing high-performance liquid chromatography analysis. Associations were tested using family-based association tests and logistical regression analysis. The alleles IL13-1055C (p = 0.05) and IL13-591A (p = 0.01) are shown, by family-based association test, to be preferentially transmitted to children with the 10% highest infections. A logistic regression analysis that included IL13-1055 G/G, G/T and T/T genotypes, age, gender, and village of residency, applied to the whole study population, showed that subjects bearing the IL13-1055T/T genotype were on average much less infected than individuals with other genotypes. Previous studies on asthma indicated that the IL13-1055T allele increased gene transcription, which is in agreement with the fact that this cytokine enhances resistance to infection by schistosome in humans.

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“…Some inflammatory genes, such as the genes encoding GM-CSF and cyclooxygenase (COX)-2, produce mRNA that is particularly susceptible to the action of ribonucleases, which break down mRNA, thus switching off protein synthesis. Corticosteroids may have inhibitory effects on the proteins that stabilise mRNA, leading to more rapid breakdown and, thus, a reduction in inflammatory protein expression [54][55][56]. Corticosteroids do not appear to have any effect on HuR or tristeraprolin expression, however [57].…”

Section: Nontranscriptional Effectsmentioning

confidence: 99%

Corticosteroid effects on cell signalling

Barnes¹

2006

European Respiratory Journal

360

245

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Corticosteroids are the most effective anti-inflammatory therapy for asthma. Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-kB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways, mainly by reversing histone acetylation of activated inflammatory genes through binding of glucocorticoid receptors to coactivators and recruitment of histone deacetylase 2 to the activated transcription complex.Activated glucocorticoid receptors also bind to recognition sites in the promoters of certain genes in order to activate their transcription, resulting in secretion of anti-inflammatory proteins, such as mitogen-activated protein kinase phosphatase-1, which inhibits mitogen-activated protein kinase signalling pathways. Glucocorticoid receptors may also interact with other recognition sites to inhibit transcription, for example of several genes linked to their side-effects.In some patients with steroid-resistant asthma, there are abnormalities in glucocorticoid receptor signalling pathways. In chronic obstructive pulmonary disease patients and asthmatic patients who smoke, histone deacetylase 2 is markedly impaired as a result of oxidative/nitrative stress, and so inflammation is resistant to the anti-inflammatory effects of corticosteroids.The therapeutic implications of these new findings are discussed.

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Molecular Regulation of Granulocyte Macrophage Colony-Stimulating Factor in Human Lung Epithelial Cells by Interleukin (IL)-1 β , IL-4, and IL-13 Involves Both Transcriptional and Post-Transcriptional Mechanisms

Cited by 52 publications

References 44 publications

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Analysis of the 5q31-q33 Locus Shows an Association between IL13-1055C/T IL-13-591A/G Polymorphisms and Schistosoma haematobium Infections

Corticosteroid effects on cell signalling

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