Ceramide and sphingosine in pulmonary infections

Seitz, Amy E.; Grassmé, Heike; Edwards, Michael J.; Pewzner-Jung, Yael; Gulbins, Erich

doi:10.1515/hsz-2014-0285

Cited by 44 publications

(35 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ceramides interfere both with proximal INSR signaling and with downstream activation of AKT by promoting activation of protein phosphatase 2A (PP2A) and PKCζ , as well as inhibiting direct phosphorylation of Akt on Ser 473 phosphorylation . Infection with both viral and bacterial pathogens has been shown to increase ceramide levels , which is involved in the development of pathology . Interestingly, whereas infection increases ceramide levels and ceramides negatively impact insulin sensitivity, it has not been formally proven that infection causes systemic IR through an increase of specific forms of ceramides.…”

Section: Infection and Diabetesmentioning

confidence: 99%

‘Beauty and the beast’ in infection: How immune–endocrine interactions regulate systemic metabolism in the context of infection

et al. 2019

View full text Add to dashboard Cite

The immune and endocrine systems ensure two vital functions in the body. The immune system protects us from lethal pathogens, whereas the endocrine system ensures proper metabolic function of peripheral organs by regulating systemic homeostasis. These two systems were long thought to operate independently. The immune system uses cytokines and immune receptors, whereas the endocrine system uses hormones to regulate metabolism. However, recent findings show that the immune and endocrine systems closely interact, especially regarding regulation of glucose metabolism. In response to pathogen encounter, cytokines modify responsiveness of peripheral organs to endocrine signals, resulting in altered levels of blood hormones such as insulin, which promotes the ability of the body to fight infection. Here we provide an overview of recent literature describing various mechanisms, which the immune system utilizes to modify endocrine regulation of systemic metabolism. Moreover, we will describe how these immuneendocrine interactions derail in the context of obesity. From a clinical perspective we will elaborate how infection and obesity aggravate the development of metabolic diseases such as diabetes mellitus type 2 in humans. In summary, this review provides a comprehensive overview of immune-induced changes in systemic metabolism following infection, with a focus on regulation of glucose metabolism.Keywords: diabetes r glucose r infection r insulin resistance r metabolic disease P. A., Lordan, J. L. et al., Ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis lung disease. Am. J.

show abstract

Section: Infection and Diabetesmentioning

confidence: 99%

‘Beauty and the beast’ in infection: How immune–endocrine interactions regulate systemic metabolism in the context of infection

et al. 2019

View full text Add to dashboard Cite

show abstract

“…PA infection activates host N ADPH ox idase (Nox) proteins (Fu et al, 2013), and acid SM (Managò et al, 2015), leading to the generation of reactive oxygen species (ROS) and ceramides, respectively. Excessive ROS and ceramide production have been implicated in lung inflammation, cell death, and susceptibility to infection in CF (Seitz et al, 2015). However, recent studies also suggest a role for ceramides and sphingosine in mounting lung defense against bacterial pathogens as targeting sphingolipid pathways suppresses the recruitment of neutrophils and other inflammatory immune cells into the lung, thereby reducing lung inflammation (ManagòAntonella et al, 2015).…”

Section: S1p/sphks/s1pl Signaling Axis In Respiratory and Lung Dismentioning

confidence: 99%

Targeting sphingosine-1-phosphate signaling in lung diseases

Ebenezer

Natarajan

2016

Pharmacology & Therapeutics

View full text Add to dashboard Cite

Sphingosine-1- phosphate (S1P), a simple, bioactive sphingolipid metabolite, plays a key role, both intracellularly and extracellularly, in various cellular processes such as proliferation, survival, migration, inflammation, angiogenesis, and endothelial barrier integrity. The cellular S1P level is low and is tightly regulated by its synthesis and degradation. Sphingosine Kinases (SphKs) 1 and 2, catalyze the ATP-dependent phosphorylation of sphingosine to S1P, while the degradation is mediated by the reversible dephosphorylation catalyzed by the S1P phosphatases and lipid phosphate phosphatases and the irreversible degradation to hexadecenal and ethanolamine phosphate by sphingosine-1-phosphate lyase (S1PL). As a ligand for specific G-protein-coupled receptors, S1P1–5, which are differentially expressed in different cell types, S1P generates downstream signals that play crucial role in developmental and disease related pathologies. In addition to acting extracellularly on receptors located on the plasma membrane, S1P can also act intracellularly, independently of S1P1–5, affecting calcium homeostasis and cell proliferation. The SphKs /S1P /S1PL metabolic pathway is implicated in numerous human pathologies including respiratory disorders, thereby raising the possibility that manipulating intracellular S1P levels could offer therapeutic potential in ameliorating lung diseases. This review focuses on the prospects of targeting S1P signaling and S1P metabolizing enzymes using small molecule inhibitors, receptor agonists, and antagonists in the treatment of lung diseases.

show abstract

“…The sphingoid base backbone sphingosine carries a natural amino group and plays a central role in infections with N. gonorrhoeae among other bacterial pathogens. 35 Addition of ω-N3-sphingosine to infected Chang cells followed by GA fixation, permeabilization, click labeling with DIBO-Alexa Fluor 488 and gelation demonstrated the general applicability of the method.…”

Section: Very Recently Boyden and Coworkers Introduced An Alternativmentioning

confidence: 97%

Nanoscale imaging of bacterial infections by sphingolipid expansion microscopy

Goetz

Kunz

Fink

et al. 2020

Preprint

View full text Add to dashboard Cite

Expansion microscopy (ExM) enables super-resolution imaging of proteins and nucleic acids on conventional microscopes. However, imaging of details of the organization of lipid bilayers by light microscopy remains challenging. We introduce an azide-and amino-modified sphingolipid ceramide, which upon incorporation into membranes can be labeled by click chemistry and linked into hydrogels, followed by 4x to 10x expansion. Confocal and structured illumination microscopy (SIM) enabled imaging of sphingolipids and their interactions with proteins in the membrane of intracellular organelles with a spatial resolution of 10-20 nm. Because sphingolipids accumulated efficiently in pathogens we used sphingolipid ExM to investigate bacterial infections of human HeLa229 cells by Neisseria gonorrhoeae, Chlamydia trachomatis and Simkania negevensis with a resolution so far only provided by electron microscopy. In particular, sphingolipid ExM allowed us to visualize the inner and outer membrane of intracellular bacteria and determine their distance to 27.6 ± 7.7 nm. The Supporting Information is available free of charge on the ACS Publications website. Supplementary Figures S1-S23. Supplementary Movie 1: 10x ExM SIM z-stack of Hela229 cells infected with Chlamydia trachomatis for 24 h, fed with α-NH2-ω-N3-C6-ceramide, fixed, permeabilized and stained with DBCO-Alexa Fluor 488. Chlamydia are clearly located at the inclusion membrane. Scale bar, 10 µm.

show abstract

Ceramide and sphingosine in pulmonary infections

Cited by 44 publications

References 65 publications

‘Beauty and the beast’ in infection: How immune–endocrine interactions regulate systemic metabolism in the context of infection

‘Beauty and the beast’ in infection: How immune–endocrine interactions regulate systemic metabolism in the context of infection

Targeting sphingosine-1-phosphate signaling in lung diseases

Nanoscale imaging of bacterial infections by sphingolipid expansion microscopy

Contact Info

Product

Resources

About