The role of sphingosine 1-phosphate in the TNF-alpha induction of IL-8 gene expression in lung epithelial cells.

Department of Molecular Biology, University of Texas Health Center at Tyler, 11937 US Highway 271 Tyler, TX 75708-3154, USA.
Gene (Impact Factor: 2.08). 05/2007; 391(1-2):150-60. DOI: 10.1016/j.gene.2006.12.011
Source: PubMed

ABSTRACT Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine involved in the pathogenesis of inflammatory diseases of the lung. Interleukin-8 (IL-8), a C-X-C chemokine, is induced by TNF-alpha and initiates injury by acting as a chemoattractant for neutrophils and other immune cells. Although sphingolipids such as ceramide and sphingosine 1-phosphate (S1-P) have been shown to serve as signaling molecules in the TNF-alpha inflammatory response, their role in the TNF-alpha induction of IL-8 gene expression in lung epithelial cells is not known. We investigated the role of sphingolipids in the TNF-alpha induction of IL-8 gene expression in H441 lung epithelial cells. We found that TNF-alpha induced IL-8 mRNA levels by increasing gene transcription, and the stability of IL-8 mRNA was not affected. Exogenous S1-P but not ceramide or sphingosine increased IL-8 mRNA levels and IL-8 secretion. Dimethylsphingosine, an inhibitor of sphingosine kinase, partially inhibited TNF-alpha induction of IL-8 mRNA levels indicating the importance of intracellular increases in S1-P in the IL-8 induction. S1-P induction of IL-8 mRNA was due to an increase in gene transcription, and the stability of IL-8 mRNA was not affected. S1-P induction of IL-8 mRNA was associated with an increase in the binding activity of AP-1 but the activities of NF-kappaB and NF IL-6 were unchanged. S1-P induced the phosphorylation of ERK, p38 and JNK MAPKs. Pharmacological inhibitors of ERK and p38 but not JNK partly inhibited S1-P induction of IL-8 mRNA levels. These data show that increases in the intracellular S1-P partly mediate TNF-alpha induction of IL-8 gene expression in H441 lung epithelial cells via ERK and p38 MAPK signaling pathways and increased AP-1 DNA binding.

Download full-text


Available from: Vijayakumar Boggaram, Jun 22, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite, which has emerged as an important signaling mediator participating in the regulation of multiple cellular processes. The discovery of a family of S1P receptors, together with the more recently identified intracellular targets, has provided fundamental understanding of the multi-faceted actions of S1P. Evidence from both in vitro and in vivo studies has implicated the S1P signaling system in the control of immunity, inflammation and many associated diseases. Enigmatically, S1P appears to have both pro- and anti-inflammatory effects depending on the cell context. Here, we review this emerging area and argue for a pivotal role for S1P, as a key mediator of the cytokine network, acting through juxtacrine signaling in the immune system.
    Cytokine & growth factor reviews 11/2010; 22(1):45-53. DOI:10.1016/j.cytogfr.2010.09.004 · 6.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Staphylococcus aureus releases virulence factors (VF) that may impair the innate protective functions of airway cells. The aim of this study was to determine whether a long-acting beta2 adrenergic receptor agonist (salmeterol hydroxynaphthoate, Sal) combined with a corticosteroid (fluticasone propionate, FP) was able to regulate ion content and cytokine expression by airway glandular cells after exposure to S. aureus supernatant. A human airway glandular cell line was incubated with S. aureus supernatant for 1 h and then treated with the combination Sal/FP for 4 h. The expression of actin and CFTR proteins was analyzed by immunofluorescence. Videomicroscopy was used to evaluate chloride secretion and X-ray microanalysis to measure the intracellular ion and water content. The pro-inflammatory cytokine expression was assessed by RT-PCR and ELISA. When the cells were incubated with S. aureus supernatant and then with Sal/FP, the cellular localisation of CFTR was apical compared to the cytoplasmic localisation in cells incubated with S. aureus supernatant alone. The incubation of airway epithelial cells with S. aureus supernatant reduced by 66% the chloride efflux that was fully restored by Sal/FP treatment. We also observed that Sal/FP treatment induced the restoration of ion (Cl and S) and water content within the intracellular secretory granules of airway glandular cells and reduced the bacterial supernatant-dependent increase of pro-inflammatory cytokines IL8 and TNFalpha. Our results demonstrate that treatment with the combination of a corticosteroid and a long-acting beta2 adrenergic receptor agonist after bacterial infection restores the airway glandular cell function. Abnormal mucus induced by defective ion transport during pulmonary infection could benefit from treatment with a combination of beta2 adrenergic receptor agonist and glucocorticoid.
    Respiratory research 01/2010; 11(1):6. DOI:10.1186/1465-9921-11-6 · 3.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes.
    International Journal of Molecular Sciences 07/2014; 15(7):12807-12841. DOI:10.3390/ijms150712807 · 2.46 Impact Factor