ArticleMolecular and cellular biology2013
A novel role of a lipid species, sphingosine-1-phosphate, in epithelial innate immunity.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 65 citations in OpenAlex.
- Sphingosine-1-Phosphate Promotes FOS Activation in Osteosarcoma Under Tumor Acidosis.Acta physiologica (Oxford, England) · 2026Article
- Small EVs From Adipose-Derived MSCs Modulate Epidermal Barrier and Inflammation Via Sphingosine-1-Phosphate Signaling Pathway.Journal of extracellular vesicles · 2025Article
- Contribution of Keratinocytes in Skin Cancer Initiation and Progression.International journal of molecular sciences · 2024Review
- Ceramide-1-phosphate alleviates high-altitude pulmonary edema by stabilizing circadian ARNTL-mediated mitochondrial dynamics.Journal of advanced research · 2024Article
- Fanning the Flames of Endoplasmic Reticulum (ER) Stress: Can Sphingolipid Metabolism Be Targeted to Enhance ER Stress-Associated Immunogenic Cell Death in Cancer?Molecular pharmacology · 2024Review
- Regulation of Host Defense Peptide Synthesis by Polyphenols.Antibiotics (Basel, Switzerland) · 2023Review
- Endoplasmic-reticulum-stress-induced lipotoxicity in human kidney epithelial cells.Toxicology research · 2022Article
- Sphingosine-1-Phosphate-Triggered Expression of Cathelicidin LL-37 Promotes the Growth of Human Bladder Cancer Cells.International journal of molecular sciences · 2022Article
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- Diesel Particulate Extract Accelerates Premature Skin Aging in Human Fibroblasts via Ceramide-1-Phosphate-Mediated Signaling Pathway.International journal of molecular sciences · 2022Article
- Ceramides in Skin Health and Disease: An Update.American journal of clinical dermatology · 2021Review
- CERKL is upregulated in cutaneous squamous cell carcinoma and maintains cellular sphingolipids and resistance to oxidative stress.The British journal of dermatology · 2021Article
- Mammalian Epidermis: A Compendium of Lipid Functionality.Frontiers in physiology · 2021Review
- S1P Generation by Sphingosine Kinase-2 in Recruited Macrophages Resolves Lung Inflammation by Blocking STING Signaling in Alveolar Macrophages.Journal of cellular signaling · 2021Article
- Lipid composition of the cancer cell membrane.Journal of bioenergetics and biomembranes · 2020Review
- SPHK2-Generated S1P in CD11bCell reports · 2020Article
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- Unbalanced Sphingolipid Metabolism and Its Implications for the Pathogenesis of Psoriasis.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
A variety of external perturbations can induce endoplasmic reticulum (ER) stress, followed by stimulation of epithelial cells to produce an innate immune element, the cathelicidin antimicrobial peptide (CAMP). ER stress also increases production of the proapoptotic lipid ceramide and its antiapoptotic metabolite, sphingosine-1-phosphate (S1P). We demonstrate here that S1P mediates ER stress-induced CAMP generation. Cellular ceramide and S1P levels rose in parallel with CAMP levels following addition of either exogenous cell-permeating ceramide (C2Cer), which increases S1P production, or thapsigargin (an ER stressor), applied to cultured human skin keratinocytes or topically to mouse skin. Knockdown of S1P lyase, which catabolizes S1P, enhanced ER stress-induced CAMP production in cultured cells and mouse skin. These and additional inhibitor studies show that S1P is responsible for ER stress-induced upregulation of CAMP expression. Increased CAMP expression is likely mediated via S1P-dependent NF-κB-C/EBPα activation. Finally, lysates of both ER-stressed and S1P-stimulated cells blocked growth of virulent Staphylococcus aureus in vitro, and topical C2Cer and LL-37 inhibited invasion of Staphylococcus aureus into murine skin. These studies suggest that S1P generation resulting in increased CAMP production comprises a novel regulatory mechanism of epithelial innate immune responses to external perturbations, pointing to a new therapeutic approach to enhance antimicrobial defense.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.