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Cited by 72Adrenal Hormones and DisordersImmune Response and InflammationStress Responses and Cortisol

Glucocorticoid pretreatment induces cytokine overexpression and nuclear factor-κB activation in macrophages

Smyth, Gordon P., Stapleton, Philip P., Freeman, Tracy A., Concannon, Erin M., Mestre, Juan R., Duff, Michael, Maddali, Sirish, Daly, John M.·2004·Journal of Surgical Research
DOI 10.1016/s0022-4804(03)00300-7
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Abstract

Background Glucocorticoids are widely used in treating inflammatory diseases. The contribution of adrenal glucocorticoids to inflammatory regulation is unknown. Endogenous glucocorticoids, as distinct from synthetic analogues, not only suppress but also enhance immune functions. Elevated circulating cortisol levels are characteristic of injured patients. In a model of trauma, an early glucocorticoid surge occurs concomitantly with decreased cellular cytokine responses. Cytokine production elevated late after injury is associated with increased mortality. We hypothesized that this glucocorticoid surge mediates the later heightened macrophage responses.Materials and methods The murine macrophage like cells RAW 264.7 were incubated with corticosterone (35 ng/mL), or vehicle control, for 1 h, after which the cells were washed and corticosterone-free medium added. At 0, 3, 6, 12, and 24 h after removal of the corticosterone, the cells were stimulated with lipopolysaccharide (LPS) and interferon-gamma. Supernatant tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and nitrite levels were measured. In separate experiments the effect of pretreatment with corticosterone on TNF-alpha, IL-6, and nitrite mRNA expression as well as nuclear factor-kappaB and glucocorticoid receptor activity was determined. CD14 receptor expression was determined by flow cytometry.Results Glucocorticoid pretreatment caused significantly increased RAW 264.7 cell production of nitrite, IL-6 and TNF-alpha. mRNA for these inflammatory mediators was induced 6 h after the corticosterone pretreatment, and was associated with activation of nuclear factor-kappaB in the presence of activated glucocorticoid receptor. Cell surface-expression of CD14 was likewise increased.Conclusions The results of this study demonstrate a novel role for glucocorticoids and provide a mechanism for the late upregulation in macrophage function after injury.

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  • In cultured macrophages, CORT treatment 24 or 12 hr prior to LPS increases LPS-induced TNF-α, IL-6, and nitrite levels, while CORT treatment at 6, 3, or 0 hr prior to LPS does not.

    “Similarly, in cultured macrophages, CORT treatment 24 or 12 hr prior to LPS increases LPS-induced TNF-α, IL-6, and nitrite levels, while CORT treatment at 6, 3, or 0 hr prior to LPS does not (Smyth et al., 2004).”

    From The Stressed CNS: When Glucocorticoids Aggravate Inflammation (2009) · cites this paper as Smyth et al., 2004

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Authors
Smyth, G. P., Stapleton, P. P., Freeman, T. A., Concannon, E. M., Mestre, J. R., Duff, M., Maddali, S., & Daly, J. M.
Affiliations
Cornell University (US)
Corresponding author
Stapleton, Philip P.
ORCID
Venue
Journal of Surgical Research
Publisher
Elsevier BV
Published
2004-02
Volume
116
Issue
2
Pages
253-261
ISSN
0022-4804 (ISSN-L)
DOI
10.1016/s0022-4804(03)00300-7
OpenAlex
W2072976282
Cited by
72
References
34
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 1
FWCI
2.33
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Surgical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
glucocorticoids, corticosterone, macrophages, cytokine expression, NF-κB activation, glucocorticoid receptor, TNF-α, interleukin-6, nitrite, CD14, lipopolysaccharide, interferon-gamma, trauma (physical injury), inflammation, RAW 264.7 macrophages
MeSH terms
Animals, Cell Line, Corticosterone, Drug Synergism, Lipopolysaccharides, Macrophages, Nitrites, Receptors, Glucocorticoid, RNA, Messenger, Tumor Necrosis Factor-alpha, Interleukin-6, Up-Regulation, Cytokines, NF-kappa B, Lipopolysaccharide Receptors, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II

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