ArticleLipids in health and disease2021
Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation.
Article in Lipids in health and disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- 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
- Metabolic, microbial, and pharmacological stimuli elicit distinct lipidomic and cytokine responses in the human placenta.Molecular human reproduction · 2026Article
- Comorbidity risk characteristics of rheumatoid arthritis in the context of depression-associated lipid metabolism.Frontiers in immunology · 2026Article
- Secretory Acid Sphingomyelinase in Children and Adolescents With Type 1 Diabetes.Journal of diabetes research · 2026Article
- Dual-Target Insight into Drug Discovery from Natural Products as Modulators of GLP-1 and the TXNIP-Thioredoxin Antioxidant System in Metabolic Syndrome.Antioxidants (Basel, Switzerland) · 2025Review
- Retinitis Pigmentosa-Associated Gene TRIM49 Regulates ULK1-Mediated Autophagy and Photoreceptor Phagocytosis by the Retinal Pigment Epithelium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitigation of nicotine-induced podocyte injury through inhibition of thioredoxin interacting protein.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- The Anti-Inflammatory Potential of Tricyclic Antidepressants (TCAs): A Novel Therapeutic Approach to Atherosclerosis Pathophysiology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lipid metabolic dysregulation-induced neuroinflammation in the pathophysiology of major depressive disorder.Frontiers in immunology · 2025Review
- Effect of subanesthetic dose of esketamine on early postoperative depression in elderly patients with Sarcopenia.Journal of orthopaedic surgery and research · 2024Article
- Metabolomic Profiling and In Vivo Antiepileptic Effect ofMetabolites · 2024Article
- Co-Treatment with Phlorotannin and Extracellular Vesicles fromAntioxidants (Basel, Switzerland) · 2024Article
- Role of CD36 in central nervous system diseases.Neural regeneration research · 2024Review
- Inhibition of the HFrontiers in immunology · 2024Article
- The role of foam cells in spinal cord injury: challenges and opportunities for intervention.Frontiers in immunology · 2024Review
- Article
- Zymosan-Induced Murine Peritonitis Is Associated with an Increased Sphingolipid Synthesis without Changing the Long to Very Long Chain Ceramide Ratio.International journal of molecular sciences · 2023Article
- Ceramide induces pyroptosis through TXNIP/NLRP3/GSDMD pathway in HUVECs.BMC molecular and cell biology · 2022Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThis study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms.
methodsLipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1β and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content.
resultsImipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1β, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-κB (NF-κB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-κB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression.
conclusionThis study demonstrated that the ASM/Cer/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-κB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.
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