ArticleAutophagy2018
The autophagy receptor SQSTM1/p62 mediates anti-inflammatory actions of the selective NR3C1/glucocorticoid receptor modulator compound A (CpdA) in macrophages.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
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- Fuelling the Fight from the Gut: Short-Chain Fatty Acids and Dexamethasone Synergise to Suppress Gastric Cancer Cells.Cancers · 2025Article
- Data Mining Approach to Melatonin Treatment in Alzheimer's Disease: New Gene TargetsInternational journal of molecular sciences · 2025Article
- Macrophages are activated toward phagocytic lymphoma cell clearance by pentose phosphate pathway inhibition.Cell reports. Medicine · 2024Article
- Targeting Immunoproteasome in Polarized Macrophages Ameliorates Experimental Emphysema Via Activating NRF1/2-P62 Axis and Suppressing IRF4 Transcription.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Sesquiterpene from Artemisia argyi seed extracts: A new anti-acute peritonitis agent that suppresses the MAPK pathway and promotes autophagy.Inflammopharmacology · 2024Article
- The Anti-Inflammatory Mechanism of Flaxseed Linusorbs on Lipopolysaccharide-Induced RAW 264.7 Macrophages by Modulating TLR4/NF-κB/MAPK Pathway.Foods (Basel, Switzerland) · 2023Article
- Compound A attenuates proinflammatory cytokine-induced endoplasmic reticulum stress in beta cells and displays beneficial therapeutic effects in a mouse model of autoimmune diabetes.Cellular and molecular life sciences : CMLS · 2022Article
- Transcriptional control of energy metabolism by nuclear receptors.Nature reviews. Molecular cell biology · 2022Review
- Classifying Integrated Signature Molecules in Macrophages of Rheumatoid Arthritis, Osteoarthritis, and Periodontal Disease: An Omics-Based Study.Current issues in molecular biology · 2022Article
- Dexamethasone Alleviates Myocardial Injury in a Rat Model of Acute Myocardial Infarction Supported by Venoarterial Extracorporeal Membrane Oxygenation.Frontiers in public health · 2022Article
- Network Pharmacological Study on the Mechanism of Cynanchum paniculatum (Xuchangqing) in the Treatment of Bungarus multicinctus Bites.BioMed research international · 2022Article
- High Level of Uric Acid Promotes Atherosclerosis by Targeting NRF2-Mediated Autophagy Dysfunction and Ferroptosis.Oxidative medicine and cellular longevity · 2022Article
- Synergistic Regulation of Microglia Gene Expression by Natural Molecules in Herbal Medicine.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- The Role of Autophagy in Skeletal Muscle Diseases.Frontiers in physiology · 2021Review
- The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model.Molecular medicine reports · 2020Article
- PPARγ Cistrome Repression during Activation of Lung Monocyte-Macrophages in Severe COVID-19.iScience · 2020Article
- Dexamethasone induces aberrant macrophage immune function and apoptosis.Oncology reports · 2020Article
- More Than Suppression: Glucocorticoid Action on Monocytes and Macrophages.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoids are widely used to treat inflammatory disorders; however, prolonged use of glucocorticoids results in side effects including osteoporosis, diabetes and obesity. Compound A (CpdA), identified as a selective NR3C1/glucocorticoid receptor (nuclear receptor subfamily 3, group C, member 1) modulator, exhibits an inflammation-suppressive effect, largely in the absence of detrimental side effects. To understand the mechanistic differences between the classic glucocorticoid dexamethasone (DEX) and CpdA, we looked for proteins oppositely regulated in bone marrow-derived macrophages using an unbiased proteomics approach. We found that the autophagy receptor SQSTM1 but not NR3C1 mediates the anti-inflammatory action of CpdA. CpdA drives SQSTM1 upregulation by recruiting the NFE2L2 transcription factor to its promoter. In contrast, the classic NR3C1 ligand dexamethasone recruits NR3C1 to the Sqstm1 promoter and other NFE2L2-controlled gene promoters, resulting in gene downregulation. Both DEX and CpdA induce autophagy, with marked different autophagy characteristics and morphology. Suppression of LPS-induced Il6 and Ccl2 genes by CpdA in macrophages is hampered upon Sqstm1 silencing, confirming that SQSTM1 is essential for the anti-inflammatory capacity of CpdA, at least in this cell type. Together, these results demonstrate how off-target mechanisms of selective NR3C1 ligands may contribute to a more efficient anti-inflammatory therapy.
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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.