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Non-genomic Effects of Glucocorticoids: An Updated View
Open accessAbstract
Glucocorticoid (GC) anti-inflammatory effects generally require a prolonged onset of action and involve genomic processes. Because of the rapidity of some of the GC effects, however, the concept that non-genomic actions may contribute to GC mechanisms of action has arisen. While the mechanisms have not been completely elucidated, the non-genomic effects may play a role in the management of inflammatory diseases. For instance, we recently reported that GCs 'rapidly' enhanced the effects of bronchodilators, agents used in the treatment of allergic asthma. In this review article, we discuss (i) the non-genomic effects of GCs on pathways relevant to the pathogenesis of inflammatory diseases and (ii) the putative role of the membrane GC receptor. Since GC side effects are often considered to be generated through its genomic actions, understanding GC non-genomic effects will help design GCs with a better therapeutic index.
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“suggesting that also the effects on synaptic transmission in the CeA are mediated via non-genomic GR signaling.”
From Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats (2022) · cites this paper as Panettieri et al., 2019
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“most non-genomic glucocorticoid effects are sensitive to mifepristone antagonism (Panettieri et al., 2019)”
From Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats (2022) · cites this paper as Panettieri et al., 2019
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From NSAIDs to Glucocorticoids and Beyond
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“ation of calcium intracellular levels, reduced smooth muscle contraction and modulation of reactive oxygen species production, are summarized elsewhere.(14) Although seldom studied in horses, the nongenomic actions of GC on neutrophils are mediated in part by the GCR.”
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“To further support this evidence, we also evaluated the transcriptional activation induced by glucocorticoid receptors, which is normally boosted after acute stress exposure due to the activation of the HPA axis and subsequent release of corticosterone [45,46].”
BackgroundEmerging nanoparticle platforms to improve the administration of glucocorticoids
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“Recent evidence indicates a more rapid onset (minutes) of action of ICS due to the complementary mechanisms of nongenomic and genomic effects 67,68 .”
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“Non-genomic mechanisms may play other roles in pulse therapy [80].”
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“[ 67 ] It has also been suggested that GCs rapidly decrease basal intracellular Ca 2 + levels by interfering with Ca 2 + cycling from intracellular stores into the cytoplasm, reducing ATP consumption and ROS production, thus affecting cellular energy metabolism.”
BackgroundBiological Therapy for Inflammatory Bowel Disease
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“The regulation of growth and metabolic and immune functions is the responsibility of glucocorticoid modulators (Panettieri et al., 2019).”
BackgroundSystemic and targeted steroids for the treatment of IgA nephropathy
Locatelli, F., Vecchio, L. D., & Ponticelli, C. E. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad224 · Cited by 18
“In this respect, intravenous megadoses of glucocorticoids may downregulate glucocorticoid receptors and exert non-genomic effects [ 14 –17 ].”
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“activity through the so-called non-genomic pathway, cytosolic receptors are internalized into the nucleus where after the binding to GREs, they control the transcription of target genes (Schoneveld et al., 2004; Panettieri et al., 2019).”
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“The primary anti-inflammatory actions appear to be mediated by the inhibition of pro-inflammatory transcription factors and the suppression of prostaglandin and interleukin synthesis.(56,57) However, long-term administrations of DEX may cause serious and undesirable ocular or systemic side effects, such as elevated IO…”
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“However, this hypothesis requires testing through clinical studies.”
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Glucocorticoid Therapy in Respiratory Illness: Bench to Bedside
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“15 These rapid transcription-independent responses likely influence substantially the overall effects of GCs.”
Is it safe to withdraw low-dose glucocorticoids in SLE patients in remission?
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“…“ non-genomic ” manner that affects several signaling pathways such as PKC, Ca 2 + /calmodulin protein kinase II, nitric oxide, mitogen-activated protein kinase, caveolin-1, RhoA/ROCK 206 ; this mechanism does not require nuclear glucocorticoid receptor-mediated transcription or translation 174 .”
Cellular Immunobiology and Molecular Mechanisms in Alloimmunity—Pathways of Immunosuppression
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“198 198-200 PI3K-AKT signaling can further be inhibited by ligand-bound GR-α .”
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“Although GC mainly acts through GR, it has been reported that GC also functions in a GR-independent manner [18 – 23].”
BackgroundCortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
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Mitogen-Activated Protein Kinase and Nuclear Hormone Receptor Crosstalk in Cancer Immunotherapy
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“Relatively few studies have investigated the translocation of GRs into mitochondria induced by GCs. Psarra et al. found that after activation by GCs, GRs can translocate not only into the nucleus but also into mitochondria (Psarra and Sekeris 2009; Panettieri et al. 2019).”
Metadata
- Authors
- Panettieri, R. A., Schaafsma, D., Amrani, Y., Koziol-White, C., Ostrom, R., & Tliba, O.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- NIHR Leicester Respiratory Biomedical Research Unit (GB)
- Chapman University (US)
- Long Island University (US)
- Corresponding author
- Tliba, Omar
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 40
- Issue
- 1
- Pages
- 38-49
- ISSN
- 0165-6147 (ISSN-L)
- PMC
- PMC7106476
- OpenAlex
- W2902671349
- Cited by
- 297
- References
- 68
- Citations by year
- 2026: 33 · 2025: 42 · 2024: 38 · 2023: 54 · 2022: 47 · 2021: 43 · 2020: 24 · 2019: 16
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Chapman University Digital Commons (Chapman University) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (7R01HL111541-07, 2P01HL114471-06, GM107094)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- glucocorticoids, non-genomic effects, anti-inflammatory mechanism, rapid onset of action, bronchodilators, allergic asthma, inflammatory diseases, glucocorticoid adverse effects, therapeutic index
- MeSH terms
- Animals, Anti-Inflammatory Agents, Glucocorticoids, Humans, Inflammation, Receptors, Glucocorticoid, Genomics
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