ArticleMolecular and cellular biology2014
An endoplasmic reticulum stress-initiated sphingolipid metabolite, ceramide-1-phosphate, regulates epithelial innate immunity by stimulating β-defensin production.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Early skin colonization byFrontiers in microbiology · 2025Article
- Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients.Orphanet journal of rare diseases · 2024Article
- Article
- 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
- The Impact of Dietary Sphingolipids on Intestinal Microbiota and Gastrointestinal Immune Homeostasis.Frontiers in immunology · 2021Review
- Mammalian Epidermis: A Compendium of Lipid Functionality.Frontiers in physiology · 2021Review
- Effect of ER stress on sphingolipid levels and apoptotic pathways in retinal pigment epithelial cells.Redox biology · 2020Article
- S-Layer Protein ofFrontiers in microbiology · 2019Article
- Insights into the role of endoplasmic reticulum stress in skin function and associated diseases.The FEBS journal · 2019Review
- Skin Barrier and Calcium.Annals of dermatology · 2018Review
- The Role of Sphingolipids on Innate Immunity to Intestinal Salmonella Infection.International journal of molecular sciences · 2017Review
- Review
- 15-Deoxy-Δ(12,14)-prostaglandin J2 Induces Apoptosis and Upregulates SOCS3 in Human Thyroid Cancer Cells.PPAR research · 2016Article
- Sphingosine-1-phosphate in inflammatory bowel disease and colitis-associated colon cancer: the fat's in the fire.Translational cancer research · 2015Article
- Role of micronutrients in skin health and function.Biomolecules & therapeutics · 2015Review
- Endoplasmic reticulum stress in intestinal epithelial cell function and inflammatory bowel disease.Gastroenterology research and practice · 2015Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Antimicrobial peptides (AMP) are ubiquitous innate immune elements in epithelial tissues. We recently discovered that a signaling lipid, the ceramide metabolite sphingosine-1-phosphate (S1P), regulates production of a major AMP, cathelicidin antimicrobial peptide (CAMP), in response to a subtoxic level of endoplasmic reticulum (ER) stress that can be induced by external perturbants in keratinocytes. We hypothesized that an ER stress-initiated signal could also regulate production of another major class of AMPs: i.e., the human beta-defensins 2 (hBD2) and 3 (hBD3). Keratinocytes stimulated with a pharmacological ER stressor, thapsigargin (Tg), increased hBD2/hBD3 as well as CAMP mRNA expression. While inhibition of sphingosine-1-phosphate production did not alter hBD expression following ER stress, blockade of ceramide-1-phosphate (C1P) suppressed Tg-induced hBD2/hBD3 but not CAMP expression. Exogenous C1P also increased hBD2/hBD3 production, indicating that C1P stimulates hBD expression. We showed further that C1P-induced hBD2/hBD3 expression is regulated by a novel pathway in which C1P stimulates downstream hBD via a cPLA2a→15d-PGJ2→PPARα/PPARβ/δ→Src kinase→STAT1/STAT3 transcriptional mechanism. Finally, conditioned medium from C1P-stimulated keratinocytes showed antimicrobial activity against Staphylococcus aureus. In summary, our present and recent studies discovered two new regulatory mechanisms of key epidermal AMP, hBD2/hBD3 and CAMP. The C1P and S1P pathways both signal to enhance innate immunity in response to ER stress.
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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.