Home LiteratureArticle Details
PMID: 14960602 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A novel antipyretic action of 15-deoxy-Delta12,14-prostaglandin J2 in the rat brain.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 24 ·No. 6 ·2004-02-11 ·Pages 1312-8

Mouihate A, Boissé L, Pittman QJ

Abstract

Fever is an important part of the host defense response, yet fever can be detrimental if it is uncontrolled. We provide the first evidence that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), can attenuate the febrile response to lipopolysaccharide (LPS) in rats via an action on the brain. Furthermore, we show that PPARgamma is expressed in the hypothalamus, an important locus in the brain for fever generation. In addition, 15d-PGJ2 and its synthesizing enzyme (PGD2 synthase) were present in rat cerebrospinal fluid, and their levels were enhanced in response to systemic injection of LPS. The antipyretic effect of 15d-PGJ2 was associated with reduction in LPS-stimulated cyclooxygenase-2 expression in the hypothalamus but not in p44/p42 mitogen-activated protein kinase phosphorylation or in the expression of the PPARgamma. Thus it is likely that there is a parallel induction of an endogenous prostanoid pathway in the brain capable of limiting deleterious actions of the proinflammatory prostaglandin E2-dependent pathway.

MeSH Terms
Analgesics, Non-Narcotic/pharmacology Animals Body Temperature/drug effects Brain/drug effects,metabolism,physiopathology Cyclooxygenase 2 Disease Models, Animal Fever/chemically induced,drug therapy,physiopathology Hypothalamus/drug effects,metabolism,physiopathology Intramolecular Oxidoreductases/cerebrospinal fluid Isoenzymes/drug effects,metabolism Lipocalins Lipopolysaccharides Male Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases/metabolism Prostaglandin D2/analogs & derivatives,cerebrospinal fluid,pharmacology Prostaglandin-Endoperoxide Synthases/drug effects,metabolism Rats Rats, Sprague-Dawley Receptors, Cytoplasmic and Nuclear/metabolism Transcription Factors/metabolism
Chemicals
15-deoxy-delta(12,14)-prostaglandin J2 Analgesics, Non-Narcotic Isoenzymes Lipocalins Lipopolysaccharides Receptors, Cytoplasmic and Nuclear Transcription Factors Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Intramolecular Oxidoreductases prostaglandin R2 D-isomerase Prostaglandin D2
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mouihate Abdeslam
Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, T2N 4N1 Canada. [email protected]
Boissé Lysa
Pittman Quentin J
References (61)
61 references, click to expand
  1. Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of inducible nitric-oxide synthase by 15-deoxy-Delta12,14-prostaglandin J2.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4668-73 PMID: 10200320
  2. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2(-/-), but not in cyclooxygenase-1(-/-) mice.
    Brain Res. 1999 Apr 17;825(1-2):86-94 PMID: 10216176
  3. Inducible cyclooxygenase may have anti-inflammatory properties.
    Nat Med. 1999 Jun;5(6):698-701 PMID: 10371510
  4. Prostanoid receptors: structures, properties, and functions.
    Physiol Rev. 1999 Oct;79(4):1193-226 PMID: 10508233
  5. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase.
    Nature. 2000 Jan 6;403(6765):103-8 PMID: 10638762
  6. Evidence for the presence of peroxisome proliferator-activated receptor (PPAR) alpha and gamma and retinoid Z receptor in cartilage. PPARgamma activation modulates the effects of interleukin-1beta on rat chondrocytes.
    J Biol Chem. 2000 Apr 21;275(16):12243-50 PMID: 10766862
  7. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway.
    Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4844-9 PMID: 10781090
  8. Feedback control of cyclooxygenase-2 expression through PPARgamma.
    J Biol Chem. 2000 Sep 8;275(36):28028-32 PMID: 10827178
  9. Anti-inflammatory actions of 15-deoxy-delta 12,14-prostaglandin J2 and troglitazone: evidence for heat shock-dependent and -independent inhibition of cytokine-induced inducible nitric oxide synthase expression.
    Diabetes. 2000 Mar;49(3):346-55 PMID: 10868955
  10. Peroxisome proliferator-activated receptor-gamma ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo.
    J Neurosci. 2000 Sep 15;20(18):6862-7 PMID: 10995830
  11. Dual MAP kinase pathways mediate opposing forms of long-term plasticity at CA3-CA1 synapses.
    Nat Neurosci. 2000 Nov;3(11):1107-12 PMID: 11036267
  12. Cellular localization of lipocalin-type prostaglandin D synthase (beta-trace) in the central nervous system of the adult rat.
    J Comp Neurol. 2000 Dec 4;428(1):62-78 PMID: 11058225
  13. Endogenous antipyretics.
    Clin Infect Dis. 2000 Oct;31 Suppl 5:S190-201 PMID: 11113023
  14. Mismatch between BDNF mRNA and protein expression in the developing visual cortex: the role of visual experience.
    Eur J Neurosci. 2001 Feb;13(4):709-21 PMID: 11207806
  15. Molecular mechanisms of fever and endogenous antipyresis.
    Ann N Y Acad Sci. 2000;917:121-34 PMID: 11268336
  16. The cyclopentone prostaglandin 15-deoxy-Delta(12,14) prostaglandin J2 represses nitric oxide, TNF-alpha, and IL-12 production by microglial cells.
    J Neuroimmunol. 2001 Apr 2;115(1-2):28-35 PMID: 11282151
  17. Cyclopentenone prostaglandins: new insights on biological activities and cellular targets.
    Med Res Rev. 2001 May;21(3):185-210 PMID: 11301410
  18. Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxin-induced fever.
    J Neurosci. 2001 Apr 15;21(8):2669-77 PMID: 11306620
  19. Inflammatory stimuli increase prostaglandin D synthase levels in cerebrospinal fluid of rats.
    Neuroreport. 2001 May 8;12(6):1161-5 PMID: 11338184
  20. Antipyretics: mechanisms of action and clinical use in fever suppression.
    Am J Med. 2001 Sep;111(4):304-15 PMID: 11566461
  21. PPAR-gamma ligands modulate effects of LPS in stimulated rat synovial fibroblasts.
    Am J Physiol Cell Physiol. 2002 Jan;282(1):C125-33 PMID: 11742805
  22. 15-deoxy-delta 12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes.
    J Biol Chem. 2002 Mar 22;277(12):10459-66 PMID: 11786541
  23. The role of PPARs in inflammation and immunity.
    J Leukoc Biol. 2002 Mar;71(3):388-400 PMID: 11867676
  24. Selective inhibition of cyclooxygenase-2 expression by 15-deoxy-Delta(12,14)(12,14)-prostaglandin J(2) in activated human astrocytes, but not in human brain macrophages.
    J Immunol. 2002 May 1;168(9):4747-55 PMID: 11971025
  25. Invited review: cytokine regulation of fever: studies using gene knockout mice.
    J Appl Physiol (1985). 2002 Jun;92(6):2648-55 PMID: 12015385
  26. Fever: beneficial and detrimental effects of antipyretics.
    Curr Opin Infect Dis. 2002 Jun;15(3):241-5 PMID: 12015457
  27. Distinct brain vascular cell types manifest inducible cyclooxygenase expression as a function of the strength and nature of immune insults.
    J Neurosci. 2002 Jul 1;22(13):5606-18 PMID: 12097512
  28. Constitutive activation of peroxisome proliferator-activated receptor-gamma suppresses pro-inflammatory adhesion molecules in human vascular endothelial cells.
    J Biol Chem. 2002 Sep 13;277(37):34176-81 PMID: 12107164
  29. Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus.
    Am J Physiol Regul Integr Comp Physiol. 2002 Sep;283(3):R800-5 PMID: 12185016
  30. Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma ) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes.
    J Biol Chem. 2002 Nov 29;277(48):46226-32 PMID: 12270934
  31. Estradiol differentially regulates lipocalin-type prostaglandin D synthase transcript levels in the rodent brain: Evidence from high-density oligonucleotide arrays and in situ hybridization.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):318-23 PMID: 12518068
  32. Endogenous interleukin-10 is required for the defervescence of fever evoked by local lipopolysaccharide-induced and Staphylococcus aureus-induced inflammation in rats.
    J Physiol. 2003 Jun 1;549(Pt 2):653-64 PMID: 12692173
  33. PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6712-7 PMID: 12740443
  34. Neuroimmune response to endogenous and exogenous pyrogens is differently modulated by sex steroids.
    Endocrinology. 2003 Jun;144(6):2454-60 PMID: 12746307
  35. Localization of PPARdelta in murine central nervous system: expression in oligodendrocytes and neurons.
    Brain Res. 2003 Jun 13;975(1-2):10-21 PMID: 12763589
  36. Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase.
    J Neurosci. 2003 Oct 29;23(30):9796-804 PMID: 14586007
  37. Fever: role of pyrogens and cryogens.
    Physiol Rev. 1991 Jan;71(1):93-127 PMID: 1986393
  38. Occurrence of 9-deoxy-delta 9,delta 12-13,14-dihydroprostaglandin D2 in human urine.
    J Biol Chem. 1988 Nov 15;263(32):16619-25 PMID: 3053696
  39. Physiological changes during thermoregulation and fever in urethan-anesthetized rats.
    Am J Physiol. 1988 Jul;255(1 Pt 2):R73-81 PMID: 3260755
  40. Purification and characterization of rat brain prostaglandin D synthetase.
    J Biol Chem. 1985 Oct 15;260(23):12410-5 PMID: 3930495
  41. Inactivation of prostaglandins E 2 and A 2 on their single passage through the pulmonary vascular bed in anaesthetized rats.
    Rev Can Biol. 1972 Dec;31(4):313-6 PMID: 4661680
  42. Changes in body temperature produced by injecting prostaglandin E1, EGTA and bacterial endotoxins into the PO-AH region and the medulla oblongata of the rat.
    Experientia. 1973;29(7):806-8 PMID: 4724705
  43. Prostaglandins A1,A2 and 19-hydroxy A1; their actions on smooth muscle and their inactivation on passage through the pulmonary and hepatic portal vascular beds.
    Br J Pharmacol. 1969 Nov;37(3):705-22 PMID: 5348473
  44. Antipyretic potency of centrally administered alpha-melanocyte stimulating hormone.
    Science. 1983 Jul 8;221(4606):192-3 PMID: 6602381
  45. Arginine vasopressin and endogenous antipyresis: evidence and significance.
    Fed Proc. 1981 Nov;40(13):2750-3 PMID: 6895360
  46. Effect of potassium-induced cortical spreading depression on prostaglandin-induced fever in conscious and urethane-anesthetized rats.
    Can J Physiol Pharmacol. 1994 Jul;72(7):716-21 PMID: 7828079
  47. Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain.
    Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9070-4 PMID: 8415655
  48. Glucocorticoids alter fever and IL-6 responses to psychological stress and to lipopolysaccharide.
    Am J Physiol. 1993 May;264(5 Pt 2):R1010-6 PMID: 8498588
  49. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.
    Cell. 1995 Dec 1;83(5):803-12 PMID: 8521497
  50. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation.
    Cell. 1995 Dec 1;83(5):813-9 PMID: 8521498
  51. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.
    Endocrinology. 1996 Jan;137(1):354-66 PMID: 8536636
  52. Cytokines and fever.
    Int Arch Allergy Immunol. 1996 Apr;109(4):301-7 PMID: 8634513
  53. Ventromedial preoptic prostaglandin E2 activates fever-producing autonomic pathways.
    J Neurosci. 1996 Oct 1;16(19):6246-54 PMID: 8815905
  54. Differential ventral septal vasopressin release is associated with sexual dimorphism in PGE2 fever.
    Am J Physiol. 1997 May;272(5 Pt 2):R1664-9 PMID: 9176362
  55. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines.
    Nature. 1998 Jan 1;391(6662):82-6 PMID: 9422509
  56. 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.
    J Neurochem. 1998 Feb;70(2):452-66 PMID: 9453538
  57. Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development.
    Endocrinology. 1998 Jun;139(6):2748-54 PMID: 9607781
  58. Brain endothelial cells express cyclooxygenase-2 during lipopolysaccharide-induced fever: light and electron microscopic immunocytochemical studies.
    J Neurosci. 1998 Aug 15;18(16):6279-89 PMID: 9698320
  59. Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3.
    Nature. 1998 Sep 17;395(6699):281-4 PMID: 9751056
  60. Vasopressin-induced antipyresis. Sex- and experience-dependent febrile responses.
    Ann N Y Acad Sci. 1998 Sep 29;856:53-61 PMID: 9917864
  61. Relationship between interleukin-1 and interleukin-1 receptor antagonist during the development of fever in the rat.
    Ann N Y Acad Sci. 1998 Sep 29;856:252-5 PMID: 9917884
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.3145-03.2004
Email
[email protected]
Published
2004-02-11
Pages
1312-8
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6730345
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.3145-03.2004 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2