ArticleThe Journal of pharmacology and experimental therapeutics2011
S-adenosylmethionine decreases lipopolysaccharide-induced phosphodiesterase 4B2 and attenuates tumor necrosis factor expression via cAMP/protein kinase A pathway.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Folic Acid Supplementation Mitigates Alzheimer's Disease by Reducing Inflammation: A Randomized Controlled Trial.Mediators of inflammation · 2016Trial
- Misoprostol modulates cytokine expression through a cAMP pathway: Potential therapeutic implication for liver disease.Clinical immunology (Orlando, Fla.) · 2015Trial
- Coordinated histone H3 methylation and acetylation regulate physiologic and pathologic fas ligand gene expression in human CD4+ T cells.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- S-adenosyl-L-methionine supplementation alleviates aortic dissection by decreasing inflammatory infiltration.Nutrition & metabolism · 2024Article
- Hepatocyte-specific mitogen-activated protein kinase phosphatase 1 in sexual dimorphism and susceptibility to alcohol induced liver injury.Frontiers in immunology · 2024Article
- Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.The Journal of pathology · 2023Article
- Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies.Biology · 2023Article
- Cyclic Nucleotide Phosphodiesterases in Alcohol Use Disorders: Involving Gut Microbiota.The international journal of neuropsychopharmacology · 2023Article
- The Efficacy of S-Adenosyl Methionine and Probiotic Supplementation on Depression: A Synergistic Approach.Nutrients · 2022Review
- The Problem of Malnutrition Associated with Major Depressive Disorder from a Sex-Gender Perspective.Nutrients · 2022Review
- Novel Liposomal Rolipram Formulation for Clinical Application to Reduce Emesis.Drug design, development and therapy · 2022Article
- Review
- Article
- Phosphodiesterase 4 Inhibition as a Therapeutic Target for Alcoholic Liver Disease: From Bedside to Bench.Hepatology (Baltimore, Md.) · 2019Article
- Challenge model of TNFJournal of pharmacokinetics and pharmacodynamics · 2019Article
- Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia.Neurobiology of disease · 2019Article
- Inflammatory pathways in alcoholic steatohepatitis.Journal of hepatology · 2019Review
- Role of lncRNAs as prognostic markers of hepatic cancer and potential therapeutic targeting by S-adenosylmethionine via inhibiting PI3K/Akt signaling pathways.Environmental science and pollution research international · 2018Article
- S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases Throughout Life.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
S-Adenosylmethionine (SAM) treatment has anti-inflammatory, cytoprotective effects against endotoxin-induced organ injury. An important component of the anti-inflammatory action of SAM involves down-regulation of the lipopolysaccharide (LPS)-induced transcriptional induction of tumor necrosis factor-α (TNF) expression by monocytes/macrophages. We examined the effect of SAM on expression and activity of LPS-induced up-regulation of phosphodiesterase 4 (PDE4), which regulates cellular cAMP levels and TNF expression. LPS treatment of RAW 264.7, a mouse macrophage cell line, led to the induction of Pde4b2 mRNA expression with no effect on Pde4a or Pde4d. SAM pretreatment led to a significant decrease in LPS-induced up-regulation of Pde4b2 expression in both RAW 264.7 cells and primary human CD14(+) monocytes. Of note, the decreased Pde4b2 mRNA expression correlated with the SAM-dependent increase in the transcriptionally repressive histone H3 lysine 9 trimethylation on the Pde4b2 intronic promoter region. The SAM-mediated decrease in LPS-inducible Pde4b2 up-regulation resulted in an increase in cellular cAMP levels and activation of cAMP-dependent protein kinase A (PKA), which plays an inhibitory role in LPS-induced TNF production. In addition, SAM did not affect LPS-inducible inhibitor of nuclear factor-κB degradation or nuclear factor-κB (NF-κB)-p65 translocation into the nucleus but rather inhibited NF-κB transcriptional activity. These results demonstrate for the first time that inhibition of LPS-induced PDE4B2 up-regulation and increased cAMP-dependent PKA activation are significant mechanisms contributing to the anti-TNF effect of SAM. Moreover, these data also suggest that SAM may be used as an effective PDE4B inhibitor in the treatment of chronic inflammatory disorders in which TNF expression plays a significant pathogenic role.
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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.