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Effect of acute systemic inflammatory response and cytokines on the transcription of the genes encoding cyclooxygenase enzymes (COX-1 and COX-2) in the rat brain.
Abstract
The aim of this study was to investigate the influence of the acute-phase response and the proinflammatory cytokines on the transcription of the genes encoding the limiting enzymes for the production of prostaglandins, cyclooxygenase (COX)-1 and COX-2, in the rat brain. The bacterial endotoxin lipopolysaccharide (intravenous and intraperitoneal) and turpentine (intramuscular) were used as different models of inflammation in adult male rats. Animals were also killed at various times after intravenous administration of interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6, and mRNAs encoding COX-1 and COX-2 were assayed by in situ hybridization histochemistry. A profound transcriptional activation of the gene encoding COX-2 was detected over blood vessels of the entire brain microvasculature, choroid plexus, and leptomeninges of lipopolysaccharide-challenged rats. Injection of the endotoxin intravenously also increased COX-2 gene expression within parvocellular division of the hypothalamic paraventricular nucleus. It is interesting that intramuscular turpentine injection stimulated transcription of COX-2 along endothelium of brain capillaries, and the signal of this transcript paralleled the inflammation of the left hind limb. A robust COX-2 mRNA signal was detected rapidly in the brain microvessels of interleukin-1beta-injected rats, whereas tumor necrosis factor-alpha administration caused a modest but significant induction of this transcript. In contrast, intravenous injection of interleukin-6 did not alter genetic expression of COX-2, and none of the above described models affected the synthesis of COX-1 gene in the rat brain. These results indicate that specific cell populations, in particular vascular- and/or perivascular-associated cells, are responsible for the central production of prostaglandins during systemic inflammation, and circulating interleukin-1beta is likely to be a potent mediator of this response.
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“However, in this latter study IL-6 did not induce COX-2 expression.”
From Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice (2003) · cites this paper as [56]
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Metadata
- Authors
- Lacroix, S., & Rivest, S.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Rivest, Serge
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1998-02
- Volume
- 70
- Issue
- 2
- Pages
- 452-466
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2063310609
- Cited by
- 280
- References
- 70
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 12 · 2012: 5
- FWCI
- 17.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- cyclooxygenase-2, cyclooxygenase-1, acute systemic inflammation, inflammatory cytokines, IL-1β, TNF-α, interleukin-6, lipopolysaccharide, turpentine, prostaglandin synthesis, cerebral microvasculature, choroid plexus, paraventricular nucleus, hypothalamus, gene transcription, neuroinflammation
- MeSH terms
- Acute Disease, Animals, Brain, Escherichia coli, Humans, Inflammation, Injections, Intramuscular, Injections, Intraperitoneal, Injections, Intravenous, Interleukin-1, Isoenzymes, Lipopolysaccharides, Male, Membrane Proteins, Paraventricular Hypothalamic Nucleus, Prostaglandin-Endoperoxide Synthases, Recombinant Proteins, RNA, Messenger, Transcription, Genetic, Tumor Necrosis Factor-alpha, Turpentine, Interleukin-6, Gene Expression Regulation, Enzymologic, Cytokines, Rats, Sprague-Dawley, Rats, Cyclooxygenase 1, Cyclooxygenase 2
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