ArticleMolecular and cellular biology2013
NF-κB1 inhibits NOD2-induced cytokine secretion through ATF3-dependent mechanisms.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Osthole induces accumulation of impaired autophagosome against pancreatic cancer cells.Scientific reports · 2024Article
- Complete Freund's adjuvant as a confounding factor in multiple sclerosis research.Frontiers in immunology · 2024Review
- ATF3 as a potential diagnostic marker of early-stage osteoarthritis and its correlation with immune infiltration through bioinformatics analysis.Bone & joint research · 2022Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response.The Journal of clinical investigation · 2021Article
- The E3 ubiquitin ligase RNF186 andProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Myeloid Cell-Intrinsic IRF5 Promotes T Cell Responses through Multiple Distinct Checkpoints In Vivo, andJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation.Cell reports · 2020Article
- LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes.Cell reports · 2019Article
- STAT3 and STAT5 Signaling Thresholds Determine Distinct Regulation for Innate Receptor-Induced Inflammatory Cytokines, andJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Reducing IRF5 expression attenuates colitis in mice, but impairs the clearance of intestinal pathogens.Mucosal immunology · 2019Article
- Twist1 and Twist2 Induce Human Macrophage Memory upon Chronic Innate Receptor Treatment by HDAC-Mediated Deacetylation of Cytokine Promoters.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Regulatory Roles of Sortilin and SorLA in Immune-Related Processes.Frontiers in pharmacology · 2018Review
- Activating transcription factor 3 in immune response and metabolic regulation.Liver research (Beijing, China) · 2017Article
- E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP.Nature communications · 2017Article
- An inflammatory bowel disease-risk variant in INAVA decreases pattern recognition receptor-induced outcomes.The Journal of clinical investigation · 2017Article
- JAK2 Disease-Risk Variants Are Gain of Function and JAK Signaling Threshold Determines Innate Receptor-Induced Proinflammatory Cytokine Secretion in Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Genetic and epigenetic regulation of intestinal fibrosis.United European gastroenterology journal · 2016Review
- Twist1 and Twist2 Contribute to Cytokine Downregulation following Chronic NOD2 Stimulation of Human Macrophages through the Coordinated Regulation of Transcriptional Repressors and Activators.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Regulation of microbially induced cytokine secretion is critical in intestinal immune homeostasis. NOD2, the Crohn's disease-associated bacterial peptidoglycan sensor, activates the NF-κB pathway. After chronic NOD2 stimulation in human macrophages, cytokine secretion is significantly attenuated, similar to the situation in the intestinal environment. We find that NF-κB1 (p105/p50) expression is upregulated with chronic NOD2 stimulation and is required for attenuation of cytokine secretion in vitro in human macrophages and in vivo in mice. Upon chronic NOD2 stimulation, regulation of both activating (H3K4Me2 and H4Ac) and inhibitory (H3K27Me3) histone modifications was observed within cytokine gene promoters; these outcomes were NF-κB1 dependent. In addition to enhanced binding to cytokine gene promoters with chronic NOD2 stimulation, NF-κB1 bound to the promoter of the transcriptional repressor, ATF3. ATF3 was then induced and bound to cytokine gene promoters; both features were impaired upon NF-κB1 knockdown. Restoring ATF3 expression under NF-κB1 knockdown conditions restored NOD2-mediated cytokine downregulation. Finally, NF-κB1 and ATF3 cooperate with other inhibitory pathways, including IRAKM and secreted mediators, to downregulate cytokine secretion after chronic NOD2 stimulation. Therefore, we identify NF-κB1 and ATF3 as critical mechanisms through which NOD2 downregulates cytokines and contributes to intestinal immune homeostasis.
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