Release of prostaglandin D<sub>2</sub> by murine mast cells: importance of metabolite formation for antiproliferative activity

Haberl, C.; Hültner, Lothar; Flügel, Andreas; Falk, M.; Geuenich, S.; Wilmanns, W.; Denzlinger, Claudio

doi:10.1080/09629359891216

Cited by 18 publications

(16 citation statements)

References 15 publications

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“…This effect disappeared in the subsequent 2 h and was followed by a pronounced anti-inflammatory activity. These results are in accordance with the hypothesis that the anti-inflammatory effect exhibited by PGD 2 is dependent on its rapid conversion by cells into the active metabolite 15dPGJ2 (Haberl et al, 1998).…”

Section: Role Of Cyclopentenones In Inflammation 91supporting

confidence: 81%

Anti-Inflammatory Activity of 15-Deoxy-Δ^12,14-PGJ₂and 2-Cyclopenten-1-one: Role of the Heat Shock Response

Ianaro¹,

Ialenti²,

Maffia³

et al. 2003

Mol Pharmacol

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The transcription factor heat shock factor 1 (HSF1) plays a key role in the expression of several genes, such as heat shock protein (hsp) genes, which are cytoprotective against several pathological conditions, including inflammation. Cyclopentenone prostaglandins (cyPG) are able to activate HSF1 and induce the synthesis of the 70-kDa hsp (hsp70) in mammalian cells. These molecules are characterized by the presence of a reactive ␣,␤-unsatured carbonyl group in the cyclopentane ring (cyclopentenone) which is the key structure for triggering HSF1 activation. In the present study, we investigated, in carrageenin hind-paw edema, an acute model of inflammation, the effect of double-stranded oligodeoxynucleotides with consensus HSF1 sequence as transcription factor decoys to inhibit HSF1 binding to native DNA sites. We show that HSF1 activation and hsp72 expression occurs in inflamed tissue and that this effect is associated with the remission of the inflammatory reaction. Moreover, we studied the effect of prostaglandin 15-deoxy-⌬ 12,14 -prostaglandin (PG) J 2 , of its precursor, PGD 2 and, for the first time in vivo, the effect of the cyclopentenone ring structure itself, 2-cyclopenten-1-one. Our results demonstrated that all agents used had anti-inflammatory properties and that this effect was associated with HSF1-induced hsp72 expression in vivo, suggesting that the use of cyclopentenone derivatives may represent a novel therapeutic approach to the treatment of inflammatory diseases.

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Section: Role Of Cyclopentenones In Inflammation 91supporting

confidence: 81%

Anti-Inflammatory Activity of 15-Deoxy-Δ^12,14-PGJ₂and 2-Cyclopenten-1-one: Role of the Heat Shock Response

Ianaro¹,

Ialenti²,

Maffia³

et al. 2003

Mol Pharmacol

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“…COX-2 mediates the synthesis of vasodilatory PGs and vasoconstrictive thromboxane A2 [37]. Vasodilatory PGs (PGE 2 and PGI 2 ) have been attributed with salutary effects associated with increases in blood flow and antiproliferative properties [38, 39]. However, recent evidence indicates that effects of PGE 2 on growth-related responses are more complex as EP1 and EP4 receptors mediate growth-related responses [40] whereas others such as EP2 fail to do so.…”

Section: Discussionmentioning

confidence: 99%

Nicotine Augments Glomerular Injury in a Rat Model of Acute Nephritis

Jaimes¹,

Tian

Joshi³

et al. 2008

Am J Nephrol

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Background/Aims: Epidemiologic studies suggest that cigarette smoke worsens the progression of renal injury in patients with glomerular diseases. The mechanisms involved have not been elucidated. These studies were designed to determine whether nicotine worsens markers of inflammation including glomerular cell proliferation and fibronectin deposition in an in vivomodel of glomerular injury. Methods: Sprague-Dawley rats were injected with anti-Thy1 antibody and given either tap water or nicotine in the drinking water until sacrifice at day 14. Fibronectin expression was measured by Western blot and immunohistochemistry. COX-2 expression was also determined by Western blot in the kidney cortex of rats treated with nicotine and in cultured human mesangial cells treated with nicotine. Results: Anti-Thy1 antibody administration resulted in a significant increase in the number of cells per glomerulus that was further increased by the administration of nicotine. In nephritic rats, the administration of nicotine significantly increased fibronectin and COX-2 expression. In cultured human mesangial cells we also demonstrated that nicotine increases COX-2 expression and activity and that COX-2 mediates mesangial cell proliferation in response to nicotine. Conclusion: Either in vivo or in vitro treatment with nicotine leads to activation of inflammatory mediators and hallmarks of glomerular injury, which may explain the mechanisms involved in the deleterious effects of cigarette smoking on renal disease.

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“…5). However, it is quite clear that when activated, the (1,43). PGD 2 is broken down into 15-d-PGJ 2 in vivo, which can then act on nearby cells recruited by the other proinflammatory factors released.…”

Section: Discussionmentioning

confidence: 99%

15-Deoxy-Δ12,1412,14-PGJ2 Induces IL-8 Production in Human T Cells by a Mitogen-Activated Protein Kinase Pathway

Harris

Smith

Phipps

2002

The Journal of Immunology

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Mast cells, platelets, and some macrophages are abundant sources of PGD2 and its active metabolite 15-deoxy-Δ12,14-PGJ2 (15-d-PGJ2). The lipid mediator 15-d-PGJ2 regulates numerous processes, including adipogenesis, apoptosis, and inflammation. The 15-d-PGJ2 has been shown to both inhibit as well as induce the production of inflammatory mediators such as TNF-α, IL-1β, and cyclooxygenase, mostly occurring via a nuclear receptor called peroxisome proliferator-activated receptor-γ (PPAR-γ). Data concerning the effects of 15-d-PGJ2 on human T cells and immune regulation are sparse. IL-8, a cytokine with both chemotactic and angiogenic effects, is produced by T lymphocytes following activation. Whether 15-d-PGJ2 can regulate the production of IL-8 in T cells in unknown. Interestingly, 15-d-PGJ2 treatment of unstimulated T cells induces cell death. In contrast, in activated human T lymphocytes, 15-d-PGJ2 does not kill them, but induces the synthesis of IL-8. In this study, we report that 15-d-PGJ2 induced a significant increase in both IL-8 mRNA and protein from activated human T lymphocytes. The induction of IL-8 by 15-d-PGJ2 did not occur through the nuclear receptor PPAR-γ, as synthetic PPAR-γ agonists did not mimic the IL-8-inducing effects of 15-d-PGJ2. The mechanism of IL-8 induction was through a mitogen-activated protein kinase and NF-κB pathway, as inhibitors of both systems abrogated IL-8 protein induction. Therefore, 15-d-PGJ2 can act as a potent proinflammatory mediator in activated T cells by inducing the production of IL-8. These findings show the complexity with which 15-d-PGJ2 regulates T cells by possessing both pro- and anti-inflammatory properties depending on the activation state of the cell. The implications of this research also include that caution is warranted in assigning a solely anti-inflammatory role for 15-d-PGJ2.

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Release of prostaglandin D₂ by murine mast cells: importance of metabolite formation for antiproliferative activity

Cited by 18 publications

References 15 publications

Anti-Inflammatory Activity of 15-Deoxy-Δ^12,14-PGJ₂and 2-Cyclopenten-1-one: Role of the Heat Shock Response

Anti-Inflammatory Activity of 15-Deoxy-Δ^12,14-PGJ₂and 2-Cyclopenten-1-one: Role of the Heat Shock Response

Nicotine Augments Glomerular Injury in a Rat Model of Acute Nephritis

15-Deoxy-Δ12,1412,14-PGJ2 Induces IL-8 Production in Human T Cells by a Mitogen-Activated Protein Kinase Pathway

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Release of prostaglandin D2 by murine mast cells: importance of metabolite formation for antiproliferative activity

Cited by 18 publications

References 15 publications

Anti-Inflammatory Activity of 15-Deoxy-Δ12,14-PGJ2and 2-Cyclopenten-1-one: Role of the Heat Shock Response

Anti-Inflammatory Activity of 15-Deoxy-Δ12,14-PGJ2and 2-Cyclopenten-1-one: Role of the Heat Shock Response

Nicotine Augments Glomerular Injury in a Rat Model of Acute Nephritis

15-Deoxy-Δ12,1412,14-PGJ2 Induces IL-8 Production in Human T Cells by a Mitogen-Activated Protein Kinase Pathway

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Product

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Release of prostaglandin D₂ by murine mast cells: importance of metabolite formation for antiproliferative activity

Anti-Inflammatory Activity of 15-Deoxy-Δ^12,14-PGJ₂and 2-Cyclopenten-1-one: Role of the Heat Shock Response

Anti-Inflammatory Activity of 15-Deoxy-Δ^12,14-PGJ₂and 2-Cyclopenten-1-one: Role of the Heat Shock Response