Effect of endotoxin treatment on the expression on cyclooxygenase-2 and prostaglandin synthases in spinal cord, dorsal root ganglia, and skin of rats

Schuligoi, Rufina; Ulcar, R; Peskar, Bernhard A.; Amann, Rainer

doi:10.1016/s0306-4522(02)00783-2

Cited by 30 publications

(19 citation statements)

References 39 publications

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“…However, the peritoneal PGE 2 level in KO mice was only slightly lower (statistically insignificant) than that in WT mice under the basal condition (Fig. 3D), suggesting that the PGE 2 produced by mPGES-1 in other sites, such as in the spinal cord and dorsal root ganglia (33), may also contribute to this response. Recently, Audoly and co-workers (44) have reported ϳ50% reduction in the basal writhing reaction in mPGES-1-null mice.…”

Section: Discussionmentioning

confidence: 93%

“…3D). Given that the reduction of the peritoneal PGE 2 level is less marked than that of the writhing response in KO mice, particularly under LPSunprimed condition, we speculate that PGE 2 produced in the spinal cord and dorsal root ganglia, in which a trace level of mPGES-1 is constitutively expressed (33), might also affect pain perception by spinal neurons. As reported previously (23,24), PGI 2 is the major prostanoid released into the peritoneal cavities of mice during the acetic acid writhing response with or without LPS priming (Fig.…”

Section: Fig 2 Mpges-1 Is An Essential Component For Pge 2 Productimentioning

confidence: 86%

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Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1

Kamei

Yamakawa

Takegoshi

et al. 2004

Journal of Biological Chemistry

265

245

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We examined the in vivo role of membrane-bound prostaglandin E synthase (mPGES)-1, a terminal enzyme in the PGE 2 -biosynthetic pathway, using mPGES-1 knockout (KO) mice. Comparison of PGES activity in the membrane fraction of tissues from mPGES-1 KO and wild-type (WT) mice indicated that mPGES-1 accounted for the majority of lipopolysaccharide (LPS)-inducible PGES in WT mice. LPS-stimulated production of PGE 2 , but not other PGs, was impaired markedly in mPGES-1-null macrophages, although a low level of cyclooxygenase-2-dependent PGE 2 production still remained. Pain nociception, as assessed by the acetic acid writhing response, was reduced significantly in KO mice relative to WT mice. This phenotype was particularly evident when these mice were primed with LPS, where the stretching behavior and the peritoneal PGE 2 level of KO mice were far less than those of WT mice. Formation of inflammatory granulation tissue and attendant angiogenesis in the dorsum induced by subcutaneous implantation of a cotton thread were reduced significantly in KO mice compared with WT mice. Moreover, collagen antibody-induced arthritis, a model for human rheumatoid arthritis, was milder in KO mice than in WT mice. Collectively, our present results provide unequivocal evidence that mPGES-1 contributes to the formation of PGE 2 involved in pain hypersensitivity and inflammation.

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Section: Discussionmentioning

confidence: 93%

Section: Fig 2 Mpges-1 Is An Essential Component For Pge 2 Productimentioning

confidence: 86%

Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1

Kamei

Yamakawa

Takegoshi

et al. 2004

Journal of Biological Chemistry

265

245

View full text Add to dashboard Cite

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“…The most abundant cells of the brain expressing mPGES-1 seems to be vascular endothelial cells, but mPGES-1 has also been demonstrated in LPS-activated microglia cells (Ikeda-Matsuo et al, 2005), ␤-amyloid-treated astrocytes (Satoh et al, 2000), postnatal cortical neurons (Echeverria et al, 2005), and postischemic cortical neurons and microglia cells (IkedaMatsuo et al, 2006). mPGES-1 has also been described in the spinal cord and dorsal root ganglia in rats after treatment with LPS (Schuligoi et al, 2003).…”

Section: Membrane Prostaglandin E Synthase-1 In Fever and Painmentioning

confidence: 96%

Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target

2007

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“…Strong evidence that IL-1␤, whose levels are highly up-regulated in the paw and in the CSF following injection of the paw with Freund adjuvant, represents a major mediator of COX-2 induction in the CNS (8). The inducibility of mPGES-1 has been extensively characterized in rat brain following treatment with IL-1␤ or lipopolysaccharide (23,24,27,48,49) and during adjuvant-induced arthritis (30). In these studies, the peak of expression of COX-2 preceded that of mPGES-1 following the induction of fever with lipopolysaccharide or the intravenous administration of IL-1␤ (8,24,27).…”

Section: Mpges-1 Induction In the Cns During Peripheral Inflammationmentioning

confidence: 99%

Carrageenan-induced Paw Edema in Rat Elicits a Predominant Prostaglandin E2 (PGE2) Response in the Central Nervous System Associated with the Induction of Microsomal PGE2 Synthase-1

Guay

Bateman

Gordon

et al. 2004

Journal of Biological Chemistry

239

168

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Peripheral inflammation involves an increase in cyclooxygenase-2 (COX-2)-mediated prostaglandin (PG) synthesis in the central nervous system (CNS), which contributes to allodynia and hyperalgesia. In the present study we have determined the changes in prostanoid tissue levels and in expression of terminal prostanoid synthases in both the CNS and inflamed peripheral tissue during carrageenan-induced paw inflammation in the rat. Prostanoid levels were measured by liquid chromatography-mass spectrometry and enzyme expression at the RNA level by quantitative PCR analysis during both the early (1-6 h) and late (12 and 24 h) phases of the inflammatory response. In the paw, the early phase was associated with increases in PGE 2 and thromboxane (TX)B 2 levels and with a peak of COX-2 expression that preceded that of microsomal prostaglandin-E 2 synthase-1 (mPGES-1). COX-2 and mPGES-1 remained elevated during the late phase, and PGE 2 continued to further increase through 24 h. The cytosolic PGE 2 synthase (cPGES) showed a small transient increase during the early phase, whereas mPGES-2 expression was not affected by inflammation. In the cerebrospinal fluid, elevated levels of PGE 2 , 6-keto-PGF 1␣ , PGD 2 , and TXB 2 were detected during the early phase. PGE 2 levels also increased in the spinal cord and, to a lesser extent, in the brain and remained elevated in both the cerebrospinal fluid and the spinal cord during the late phase. The expression of mPGES-1 was strongly up-regulated in the brain and spinal cord during inflammation, whereas no change was detected for the expression of cPGES, mPGES-2, COX-1, and terminal PGD, TX, or PGI synthases. The results show that the carrageenan-induced edema in the paw elicits an early phase of COX-2 induction in the CNS leading to an increase synthesis in PGD 2 , 6-keto-PGF 1␣ , and TXB 2 in addition to the major PGE 2 response. The data also indicate that the up-regulation of mPGES-1 contributes to COX-2-mediated PGE 2 production in the CNS during peripheral inflammation.Carrageenan-induced inflammation in the rat paw represents a classical model of edema formation and hyperalgesia, which has been extensively used in the development of nonsteroidal anti-inflammatory drugs and selective COX 1 -2 inhibitors. Several lines of evidence indicate that the COX-2-mediated increase in prostaglandin (PG) E 2 production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses in this model. COX-2 is rapidly induced in the spinal cord and other regions of the CNS following carrageenan injection in the paw (1). The administration of selective COX-2 inhibitors, but not COX-1 inhibitors, reduces the levels of PGE 2 in the cerebrospinal fluid (CSF) and hyperalgesia (2-5). In addition, it has been shown that the intrathecal administration of PGE 2 potentiates carrageenaninduced inflammation (6) and that the direct microinjection of PGE 2 in the brain causes hyperalgesia (7). Selective COX-2 inhibitors can also inhibit peripheral pain responses when g...

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Effect of endotoxin treatment on the expression on cyclooxygenase-2 and prostaglandin synthases in spinal cord, dorsal root ganglia, and skin of rats

Cited by 30 publications

References 39 publications

Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1

Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1

Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target

Carrageenan-induced Paw Edema in Rat Elicits a Predominant Prostaglandin E2 (PGE2) Response in the Central Nervous System Associated with the Induction of Microsomal PGE2 Synthase-1

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