ArticleMolecular endocrinology (Baltimore, Md.)2010
Dehydroepiandrosterone sulfate directly activates protein kinase C-beta to increase human neutrophil superoxide generation.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
22 citing papers in PubMed, 69 citations in OpenAlex.
- Trial
- Low serum levels of dehydroepiandrosterone sulfate and testosterone in Albanian female patients with allergic disease.Scientific reports · 2021Trial
- Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity.Critical care (London, England) · 2018Trial
- Anti-aging effects of the adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanisms of action and beneficial effects in older people.Endocrine journal · 2026Review
- The Similarities and Differences between the Effects of Testosterone and DHEA on the Innate and Adaptive Immune Response.Biomolecules · 2022Review
- Neuroendocrine Modulation of the Immune Response after Trauma and Sepsis: Does It Influence Outcome?Journal of clinical medicine · 2020Review
- Mapping the Steroid Response to Major Trauma From Injury to Recovery: A Prospective Cohort Study.The Journal of clinical endocrinology and metabolism · 2020Observational
- Estradiol Metabolism: Crossroads in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2019Review
- Dehydroepiandrosterone: a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient.Burns & trauma · 2019Review
- Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions.Biogerontology · 2018Review
- Immunological aspects of age-related diseases.World journal of biological chemistry · 2017Review
- The influence of sex steroid hormones on the response to trauma and burn injury.Burns & trauma · 2017Review
- The Regulation of Steroid Action by Sulfation and Desulfation.Endocrine reviews · 2015Review
- Role of serum dehydroepiandrosterone sulfate level on the clearance of chronic hepatitis B virus infection.Journal of gastroenterology · 2014Article
- Bereavement reduces neutrophil oxidative burst only in older adults: role of the HPA axis and immunesenescence.Immunity & ageing : I & A · 2014Article
- Association of adrenal function and disease severity in community-acquired pneumonia.PloS one · 2014Article
- Age-dependent dysregulation of innate immunity.Nature reviews. Immunology · 2013Review
- Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake.American journal of physiology. Endocrinology and metabolism · 2013Article
- Depressive symptoms are associated with reduced neutrophil function in hip fracture patients.Brain, behavior, and immunity · 2013Article
- DHEA-S inhibits human neutrophil and human airway smooth muscle migration.Biochimica et biophysica acta · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in the human circulation and is secreted by the adrenals in an age-dependent fashion, with maximum levels during the third decade and very low levels in old age. DHEAS is considered an inactive metabolite, whereas cleavage of the sulfate group generates dehydroepiandrosterone (DHEA), a crucial sex steroid precursor. However, here we show that DHEAS, but not DHEA, increases superoxide generation in primed human neutrophils in a dose-dependent fashion, thereby impacting on a key bactericidal mechanism. This effect was not prevented by coincubation with androgen and estrogen receptor antagonists but was reversed by the protein kinase C inhibitor Bisindolylmaleimide 1. Moreover, we found that neutrophils are unique among leukocytes in expressing an organic anion-transporting polypeptide D, able to mediate active DHEAS influx transport whereas they did not express steroid sulfatase that activates DHEAS to DHEA. A specific receptor for DHEAS has not yet been identified, but we show that DHEAS directly activated recombinant protein kinase C-beta (PKC-beta) in a cell-free assay. Enhanced PKC-beta activation by DHEAS resulted in increased phosphorylation of p47(phox), a crucial component of the active reduced nicotinamide adenine dinucleotide phosphate complex responsible for neutrophil superoxide generation. Our results demonstrate that PKC-beta acts as an intracellular receptor for DHEAS in human neutrophils, a signaling mechanism entirely distinct from the role of DHEA as sex steroid precursor and with important implications for immunesenescence, which includes reduced neutrophil superoxide generation in response to pathogens.
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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.