Protective effects of a peroxisome proliferator-activated receptor-β/δ agonist in experimental autoimmune encephalomyelitis

Polak, Paul; Kalinin, Sergey; Russo, Cinzia Dello; Gavrilyuk, Vitaliy; Sharp, Anthony; Peters, Jeffrey M.; Richardson, Jill C.; Willson, Timothy M.; Weinberg, Guy; Feinstein, Douglas L.

doi:10.1016/j.jneuroim.2005.07.006

Cited by 115 publications

(116 citation statements)

References 51 publications

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“…PPARg agonists were found to inhibit the release of pro-inflammatory cytokines by microglial cells and astrocytes (Storer et al 2005). Antiinflammatory action of PPARb agonists has also been demonstrated in these cells (Polak et al 2005) and in a model of focal cerebral ischemia (Arsenijevic et al 2006). Our recent findings show for the first time that MC4R activation modulates PPAR expression in glial cells.…”

Section: Mechanisms Of Mc4r-mediated Effectsmentioning

confidence: 98%

Astrocytes: new targets of melanocortin 4 receptor actions

Caruso¹,

Carniglia²,

Durand³

et al. 2013

Journal of Molecular Endocrinology

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Astrocytes exert a wide variety of functions with paramount importance in brain physiology. After injury or infection, astrocytes become reactive and they respond by producing a variety of inflammatory mediators that help maintain brain homeostasis. Loss of astrocyte functions as well as their excessive activation can contribute to disease processes; thus, it is important to modulate reactive astrocyte response. Melanocortins are peptides with well-recognized anti-inflammatory and neuroprotective activity. Although melanocortin efficacy was shown in systemic models of inflammatory disease, mechanisms involved in their effects have not yet been fully elucidated. Central anti-inflammatory effects of melanocortins and their mechanisms are even less well known, and, in particular, the effects of melanocortins in glial cells are poorly understood. Of the five known melanocortin receptors (MCRs), only subtype 4 is present in astrocytes. MC4R has been shown to mediate melanocortin effects on energy homeostasis, reproduction, inflammation, and neuroprotection and, recently, to modulate astrocyte functions. In this review, we will describe MC4R involvement in anti-inflammatory, anorexigenic, and anti-apoptotic effects of melanocortins in the brain. We will highlight MC4R action in astrocytes and discuss their possible mechanisms of action. Melanocortin effects on astrocytes provide a new means of treating inflammation, obesity, and neurodegeneration, making them attractive targets for therapeutic interventions in the CNS.

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Section: Mechanisms Of Mc4r-mediated Effectsmentioning

confidence: 98%

Astrocytes: new targets of melanocortin 4 receptor actions

Caruso¹,

Carniglia²,

Durand³

et al. 2013

Journal of Molecular Endocrinology

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“…However, recent studies showed that GW-0742, which is a specific agonist for, reduced EAE disease severity in a receptor-dependent manner (Polak et al, 2005). In addition, GW-501516 and L-165041 can inhibit EAE by reducing IFN-γ and IL-17 secretion, suggesting a possible regulatory function for PPARβ/δ in T-cell differentiation (Kanakasabai et al, 2010).…”

Section: Ppars In T Cells and Autoimmunitymentioning

confidence: 99%

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

Choi¹,

Bothwell

2012

Molecules and Cells

149

111

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Members of the nuclear receptor superfamily function as transcription factors involved in innate and adaptive immunity as well as lipid metabolism. These highly conserved proteins participate in ligand-dependent or -independent regulatory mechanisms that affect gene expression. Peroxisome proliferator-activated receptors (PPARs), which include PPARα, PPARβ/δ, and PPARγ, are a group of nuclear receptor proteins that play diverse roles in cellular differentiation, development, and metabolism. Each PPAR subfamily is activated by different endogenous and synthetic ligands. Recent studies using specific ligand treatments and cell type-specific PPAR knockout mice have revealed important roles for these proteins in T-cell-related autoimmune diseases. Moreover, PPARs have been shown to regulate T-cell survival, activation, and CD4 + T helper cell differentiation into the Th1, Th2, Th17, and Treg lineages. Here, we review the studies that provide insight into the important regulatory roles of PPARs in T-cell activation, survival, proliferation, differentiation, and autoimmune disease.

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“…To remove any contaminating genomic DNA, total RNA was digested with DNase. Semiquantitative RT-PCR was carried out as described earlier using oligo(dT) [12][13][14][15][16][17][18] as primer and Moloney murine leukemia virus reverse transcriptase (Clontech) in a 20-l reaction mixture. The resulting cDNA was appropriately diluted, and diluted cDNA was amplified using Titanium Taq polymerase and the following primers: human primers: hMBP: sense, 5Ј-GGA AAC CAC GCA GGC AAA CGA GA-3Ј; antisense, 5Ј-GAA AAG AGG CGG ATC AAG TGG GG-3Ј; hPLP: sense, 5Ј-CTT CCC TGG TGG CCA CTG GAT TGT-3; antisense, 5Ј-TGA TGT TGG CCT CTG GAA CCC CTC-3Ј; hMOG: sense, 5Ј-TCC TCC TCC TCC TCC AAG TGT CT-3Ј; antisense, 5Ј-AGT GGG GAT CAA AAG TCC GGT GG-3Ј; hCNPase: sense, 5Ј-GGC CAC GCT GCT AGA GTG CAA GAC-3Ј; antisense, 5Ј-GGT ACT GGT ACT GGT CGG CCA TTT-3Ј; hGFAP: sense, 5Ј-TGA GTC GGT GGA GGA GGA GAT-3Ј; antisense, 5Ј-TAG TCG TTG GCT TCG TGC TTG-3Ј; hCD11b: sense, 5Ј-CAA CCA AAG GGG CAG CCT CTA CCA G-3Ј; antisense, 5Ј-CTG GGA TGA TGC TAC CAG ACC ATC-3Ј; hPPAR-␣: sense, 5Ј-CCA GTA TTT AGG ACG CTG TCC-3Ј; antisense, 5Ј-AAG TTC TTC AAG TAG GCC TCG-3Ј; PPAR-␥: sense, 5Ј-TCT CTC CGT AAT GGA AGA CC-3Ј; antisense, 5Ј-GCA TTA TGA GAC ATC CCC AC-3; hPPAR-␤: sense, 5Ј-CTG AGG TCC GGG AAG AGG AGG AGA A-3Ј; antisense, 5Ј-GCG CTC ACA CTT CTC GTA CTC CAG C-3Ј; hGAPDH: sense: 5Ј-GTT GTC ATT GTT GTG AGC CG-3; antisense, 5Ј-CAT CAC AGC CAT GAT GTT GC-3Ј; mouse primers: mouse MOG: sense, 5Ј-CCT CTC CCT TCT CCT CCT TC-3Ј; antisense, 5Ј-AGA GTC AGC ACA CCG GGG TT-3Ј; mPLP: sense, 5Ј-CTT CCC TGG TGG CCA CTG GAT TGT-3Ј; antisense, 5Ј-CCG CAG ATG GTG GTC TTG TAG TCG-3Ј; mGAPDH: sense, 5Ј-CAG GGG ATG ATC ATG GCT TCT CC-3Ј; antisense, 5Ј-GAT GCT CAC AAG AGC CCC GTT AGC-3Ј; mGAPDH: sense, 5Ј-GGT GAA GGT CGG AGT CAA CG-3Ј; antisense, 5Ј-GTG AAG ACG CCA GTG GAC TC-3Ј.…”

Section: Isolation Of Human Mixed Glial Cultures and Primarymentioning

confidence: 99%

“…PPAR-␣ is implicated in the regulation of lipid metabolism, whereas PPAR-␥ plays important roles in proliferation and differentiation of adipose cells and regulation of inflammation in many cell types including brain cells (10 -14). On the other hand, PPAR-␤ participates in diabetes, dyslipidemia, cell proliferation, and tumorigenesis (6,(15)(16)(17)(18)(19).…”

mentioning

confidence: 99%