ArticleCell death & disease2016
Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Loss of Acid Ceramidase in Myeloid Cells Protects From Chronic Colitis in IL10-Deficient Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A Nominally Safe Dose of Fumonisins Induces Mild Neuroinflammation in Chickens by Targeting Sphingolipids and Oxylipins but Not Cytokines.Antioxidants (Basel, Switzerland) · 2026Article
- Targeted analysis of sphingolipids and cytokines in plasma of dairy cows after calving reveals distinct impacts of systemic inflammation, ketosis, and mastitis.Journal of animal science and biotechnology · 2026Article
- Sphingolipids: Less Enigmatic but Still Many Questions about the Role(s) of Ceramide in the Synthesis/Function of the Ganglioside Class of Glycosphingolipids.International journal of molecular sciences · 2024Review
- The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease.Nature communications · 2024Article
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- Current advancements and future perspectives of long noncoding RNAs in lipid metabolism and signaling.Journal of advanced research · 2023Review
- Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer.Microbiome · 2023Observational
- The chromosome-scale genome of the raccoon dog: Insights into its evolutionary characteristics.iScience · 2022Article
- Chemically Induced Colitis-Associated Cancer Models in Rodents for Pharmacological Modulation: A Systematic Review.Journal of clinical medicine · 2022Review
- Review
- Calcitriol ameliorates damage in high-salt diet-induced hypertension: Evidence of communication with the gut-kidney axis.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Ceramide signaling in the gut.Molecular and cellular endocrinology · 2022Review
- Glycyrrhizic Acid Alleviates Lipopolysaccharide (LPS)-Induced Acute Lung Injury by Regulating Angiotensin-Converting Enzyme-2 (ACE2) and Caveolin-1 Signaling Pathway.Inflammation · 2022Article
- The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.Frontiers in oncology · 2022Review
- Ceramides and sphingosine-1-phosphate mediate the distinct effects of M1/M2-macrophage infusion on liver recovery after hepatectomy.Cell death & disease · 2021Article
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
- LncRNA KCNQ1OT1 inhibits the radiosensitivity and promotes the tumorigenesis of hepatocellular carcinoma via the miR-146a-5p/ACER3 axis.Cell cycle (Georgetown, Tex.) · 2020Article
- Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration.Cells · 2020Review
- Targeting alkaline ceramidase 3 alleviates the severity of nonalcoholic steatohepatitis by reducing oxidative stress.Cell death & disease · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C(18:1)-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C(18:1)-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C(18:1)-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C(18:1)-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C(18:1)-ceramide, a potent pro-inflammatory bioactive lipid and that dysregulation of ACER3 and C(18:1)-ceramide may contribute to the pathogenesis of inflammatory diseases including cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.