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Induction of micros...
Induction of microsomal prostaglandin E synthase in the rat brain endothelium and parenchyma in adjuvant-induced arthritis
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- Engblom, David, 1975- (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Ek, Monica (author)
- Karolinska Institutet
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- Andersson, Ingela (author)
- Department of Medicine, Unit of Rheumatology, The Karolinska Institute, Stockholm, Sweden
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- Saha, Sipra (author)
- Center for Structural Biochemistry, The Karolinska Institute, Huddinge, Sweden
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- Dahlström, Marie (author)
- Department of Medicine, Unit of Rheumatology, The Karolinska Institute, Stockholm, Sweden
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- Jakobsson, Per-Johan (author)
- Karolinska Institutet
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- Ericsson-Dahlstrand, Anders (author)
- 5 AstraZeneca R&D - Södertälje, Molecular Sciences, Novum, Huddinge, Sweden
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- Blomqvist, Anders, 1949- (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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(creator_code:org_t)
- 2002-09-25
- 2002
- English.
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In: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 452:3, s. 205-214
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Although central nervous symptoms such as hyperalgesia, fatigue, malaise, and anorexia constitute major problems in the treatment of patients suffering from chronic inflammatory disease, little has been known about the signaling mechanisms by which the brain is activated during such conditions. Here, in an animal model of rheumatoid arthritis, we show that microsomal prostaglandin E-synthase, the inducible terminal isomerase in the prostaglandin E2-synthesizing pathway, is expressed in endothelial cells along the blood-brain barrier and in the parenchyma of the paraventricular hypothalamic nucleus. The endothelial cells but not the paraventricular hypothalamic cells displayed a concomitant induction of cyclooxygenase-2 and expressed interleukin-1 type 1 receptors, which indicates that the induction is due to peripherally released cytokines. In contrast to cyclooxygenase-2, microsomal prostaglandin E synthase had very sparse constitutive expression, suggesting that it could be a target for developing drugs that will carry fewer side effects than the presently available cyclooxygenase inhibitors. These findings, thus, suggest that immune-to-brain communication during chronic inflammatory conditions involves prostaglandin E2-synthesis both along the blood-brain barrier and in the parenchyma of the hypothalamic paraventricular nucleus and point to novel avenues for the treatment of the brain-elicited disease symptoms during these conditions.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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