Differential Regulation of Chemokine Gene Expression by 15-Deoxy-Δ12,1412,14 Prostaglandin J2

Zhang, Xia; Wang, Ji Ming; Mukaida, Naofumi; Young, Howard A.

doi:10.4049/jimmunol.166.12.7104

Cited by 91 publications

(86 citation statements)

References 34 publications

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“…It is important to note that in previous studies from our laboratory using purified microglia, we demonstrated that PPAR-␥ agonists attenuated IL-12 p40 production in response to S. aureus stimulation (18). In addition, we noted that PPAR-␥ agonists either had no effect or exacerbated CXCL2 production in primary microglia and astrocytes following S. aureus treatment, respectively (18,19), the latter finding in agreement with other reports (74,75). In summary, we propose that although PPAR-␥ agonists have demonstrable effects on purified cell populations, these differences do not necessarily translate to the in vivo situation where a complex array of cell populations are encountered.…”

Section: Discussionsupporting

confidence: 82%

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Kielian

Syed

Liu

et al. 2008

The Journal of Immunology

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Brain abscesses result from a pyogenic parenchymal infection commonly initiated by Gram-positive bacteria such as Staphylococcus aureus. Although the host immune response elicited following infection is essential for effective bacterial containment, this response also contributes to the significant loss of brain parenchyma by necrosis that may be reduced by modulating the inflammatory response. Ciglitazone, a PPAR-γ agonist with anti-inflammatory properties, was evaluated for its ability to influence the course of brain abscess development when treatment was initiated 3 days following infection. Interestingly, abscess-associated bacterial burdens were significantly lower following ciglitazone administration, which could be explained, in part, by the finding that ciglitazone enhanced S. aureus phagocytosis by microglia. In addition, ciglitazone attenuated the expression of select inflammatory mediators during brain abscess development including inducible NO synthase, TNF-α, IL-1β, CXCL2, and CCL3. Unexpectedly, ciglitazone also accelerated brain abscess encapsulation, which was typified by the heightened expression of fibronectin and α-smooth muscle actin-positive myofibroblasts. Collectively, through its ability to attenuate excessive inflammation and accelerate abscess encapsulation, ciglitazone may effectively sequester brain abscesses and limit bacterial dissemination.

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Section: Discussionsupporting

confidence: 82%

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Kielian

Syed

Liu

et al. 2008

The Journal of Immunology

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“…Although earlier studies had shown that 15d-PGJ 2 exhibits potent anti-inflammatory effect by directly inhibiting I B kinase and NF-B through covalent modification (9 -12), the concentrations required are much higher than those detected in the inflammatory fluids (1). Furthermore, at such high concentrations, 15d-PGJ 2 can induce the expression of proinflammatory cytokines (21)(22)(23), challenging the notion that 15d-PGJ 2 has a feedback inhibitory function in the resolution of inflammation. Nevertheless, several recent studies using animal disease models have demonstrated in vivo the beneficial effect of 15d-PGJ 2 (19,32,33).…”

Section: Discussionmentioning

confidence: 94%

“…However, some recent studies have revealed that 15d-PGJ 2 at concentrations (Ͼ2 M) required to elicit direct inhibition of NF-B activation would induce the expression of proinflammatory cytokines, such as interleukin-8, and potentiate the inflammatory response (21)(22)(23). To resolve this apparent contradiction, it is important to explore the possibility that 15d-PGJ 2 at lower concentrations can exert anti-inflammatory function through alternate mechanisms.…”

Section: -mentioning

confidence: 99%

Induction of Heme Oxygenase-1 Expression in Murine Macrophages Is Essential for the Anti-inflammatory Effect of Low Dose 15-Deoxy-Δ12,14-prostaglandin J2

Lee

Tsai

Chau

2003

Journal of Biological Chemistry

205

131

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15-Deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a cyclopentenone prostaglandin, displays a potent anti-inflammatory effect at micromolar concentrations (>2 M) through direct inhibition of nuclear factor (NF)-B activation. Here we show that at submicromolar concentrations (0.1-0.5 M) 15d-PGJ 2 retains the ability to suppress the production of tumor necrosis factor-␣ (TNF-␣) and nitric oxide (NO) in lipopolysaccharide (LPS)-activated murine J774 macrophages under the conditions of a prolonged incubation (>12 h). Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1), was induced and coincident with the anti-inflammatory action of 15d-PGJ 2 . Inhibition of HO-1 activity or scavenging carbon monoxide (CO), a byproduct derived from heme degradation, significantly attenuated the suppressive activity of 15d-PGJ 2 . Furthermore, LPS-induced NF-B activation assessed by the inhibitory protein of NF-B (I B) degradation and p50 nuclear translocation was diminished in cells subjected to prolonged treatment with the low concentration of 15d-PGJ 2 . Treatment of cells with the protein synthesis inhibitor, cycloheximide, or the specific p38 MAP kinase inhibitor, SB203580, blocked the induction of HO-1 and suppression of LPS-induced I B degradation mediated by 15d-PGJ 2 . Likewise, HO inhibitor and CO scavenger were effective in abolishing the inhibitory effects of 15d-PGJ 2 on NF-B activation induced by LPS. The functional role of CO was further demonstrated by the use of a CO releasing molecule, tricarbonyldichlororuthenium(II) dimer, which significantly suppressed LPS-induced nuclear translocation of p50 as assessed by confocal immunofluorescence. Collectively, these data suggest that even at submicromolar concentrations 15d-PGJ 2 can exert an anti-inflammatory effect in macrophages through a mechanism that involves the action of HO/CO.15-Deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), 1 a dehydration product of prostaglandin D 2 , has been shown to be present in the inflammatory exudates and is increased during the resolution phase of inflammation (1). The biological effects of 15d-PGJ 2 have attracted considerable interest in recent years. It was initially identified as a high affinity natural ligand for the peroxisome proliferator-activated receptor-␥ (PPAR␥) and shown to exert several effects through binding to this nuclear receptor (2-5). More recently, several recent studies have shown that 15d-PGJ 2 exhibits a potent anti-inflammatory effect by attenuating the expression of proinflammatory mediators in activated monocytes/macrophages mainly through the inhibition of NF-B-dependent transcription of inflammatory genes (6, 7). In addition to antagonizing the NF-B activity through PPAR␥-dependent mechanism (6 -8), 15d-PGJ 2 can directly inhibit the signaling steps leading to NF-B activation (9 -12). It has also been shown that the ␣,␤-unsaturated carbonyl group of 15d-PGJ 2 can act as an electrophile to react covalently with specific cysteine residues located in the activa...

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“…The effects of PPAR-γ on chemokine expression have not been thoroughly investigated. These receptor agonists attenuate the expression of the monocyte chemoattractant MCP-1 [29,49], as well as IP-10 (CXCL3), Mig (CXCL3), and I-TAC (CXCL3) which are chemotactic for T cells [33]. Collectively, these studies suggest that PPAR-γ agonists may play an important role in mediating the migration of monocyte/macrophages and T cells into the CNS as well as retaining these cells and microglia at sites of CNS inflammation.…”

Section: Ppar-γ: Effects On Peripheral Leukocytesmentioning

confidence: 89%

Hormone regulation of microglial cell activation: relevance to multiple sclerosis

Drew

Storer

et al. 2005

Brain Research Reviews

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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of proteins. The role of PPARs in regulating the transcription of genes involved in glucose and lipid metabolism has been extensively characterized. Interestingly, PPARs have also been demonstrated to mediate inflammatory responses.Microglia participate in pathology associated with multiple sclerosis (MS). Upon activation, microglia produce molecules including NO and TNF-α that can be toxic to CNS cells including myelin-producing oligodendrocytes and neurons, which are compromised in the course of MS.Previously, we and others demonstrated that PPAR-γ agonists including 15d-PGJ 2 are effective in the treatment of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. PPAR-γ modulation of EAE may occur, at least in part, by inhibition of microglial cell activation. Here, we indicate that 15d-PGJ 2 is a more potent inhibitor of microglial activation than thiazolidinediones, which are currently used to treat diabetes. Furthermore, 15d-PGJ 2 acts cooperatively with 9-cis retinoic acid, the ligand for the retinoid X receptor (RXR), in inhibiting microglial cell activation. This suggests that 15d-PGJ 2 and 9-cis RA inhibit cell activation through the formation of PPAR-γ/ RXR heterodimers. Interestingly, PGA 2 , which like 15d-PGJ 2 is a cyclopentenone prostaglandin, but which unlike 15d-PGJ 2 does not bind PPAR-γ, is a potent inhibitor of microglial cell activation. Collectively, these studies suggest that 15d-PGJ 2 inhibits microglial cell activation by PPAR-γ-dependent as well as PPAR-γ-independent mechanisms. The studies further suggest that the PPAR-γ agonist 15d-PGJ 2 in combination with retinoids may be effective in the treatment of MS.

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Differential Regulation of Chemokine Gene Expression by 15-Deoxy-Δ12,1412,14 Prostaglandin J2

Cited by 91 publications

References 34 publications

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses

Induction of Heme Oxygenase-1 Expression in Murine Macrophages Is Essential for the Anti-inflammatory Effect of Low Dose 15-Deoxy-Δ12,14-prostaglandin J2

Hormone regulation of microglial cell activation: relevance to multiple sclerosis

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