13-Oxo-ODE is an endogenous ligand for PPARγ in human colonic epithelial cells

Altmann, Reinhold; Hausmann, Martin; Spöttl, T.; Gruber, Michael; Bull, Arthur W.; Menzel, K.; Vogl, Daniela; Herfarth, Hans H; Schölmerich, Jürgen; Falk, Werner; Rogler, Gerhard

doi:10.1016/j.bcp.2007.05.027

Cited by 114 publications

(81 citation statements)

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“…Both 9-HODE and 13-HODE are produced by cyclooxygenase and/or lipoxygenase in mammalian cells such as endothelial, epithelial, and smooth muscle cells, as well as blood cells including neutrophils, basophils, monocytes, and lymphocytes. [23][24][25][26] It has been reported that PPARg is acti- (2) (A) pPPREx3-TK-luc and pCMX-bgal were transfected into HEK293 cells together with pCMX-PPARg1. 20 h after the transfection, the cells were treated with EPA; eicosapentaenoic acid, LA; linoleic acid, OA; oleic acid, SA; stearic acid, 13-HODE, 9-HODE, 13-E,E-HODE (1) and 9-E,E-HODE (2) at the concentration of 40 mM for 20 h. Troglitazone (TGZ) was used at 5 mM.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor .GAMMA. Ligands Isolated from Adlay Seed (Coix lacryma-jobi L. var. ma-yuen STAPF.)

Yokoi

Mizukami

Nagatsu

et al. 2009

Biological & Pharmaceutical Bulletin

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Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor .GAMMA. Ligands Isolated from Adlay Seed (Coix lacryma-jobi L. var. ma-yuen STAPF.)

Yokoi

Mizukami

Nagatsu

et al. 2009

Biological & Pharmaceutical Bulletin

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“…However, Dwarakanth and colleagues (8) recently showed that 13-hydroperoxyoctadecadienoic acid (13-HPODE) (an oxidized metabolite of 12/15-lipoxygenase), which could activate PPAR␥ (22), was able to induce by itself the overexpression of MCP-1 in vascular smooth muscle cells. But in the presence of a pro-inflammatory cytokine such as TNF-␣, oxidized lipids (13-hydroxyoctadecadienoic acid, 13-oxooctadecadienoic acid, and 15-HETE) recognized by PPAR␥ inhibit TNF-␣-induced chemokine production (1). In other words, it appears that some oxidized lipids recognized by PPAR␥, when used alone are rather pro-inflammatory, while they exert anti-inflammatory actions by transrepression, when combined with strong activators of NFB (as TNF-␣).…”

Section: Discussionmentioning

confidence: 99%

“…However, responses of endothelial cells were more variable, depending on the cell strain and the extracellular matrix used (26,27). The role of specific LPA-receptors in cell migration has also been studied in Jurkat T cells where a limited role for LPA 1 and a major role for LPA 2 in cell migration were observed using a trans-Matrigel migration assay (45). Finally, Shida et al (34) found that LPA was a strong chemoattractant for human colon carcinoma DLD1 cells that express exclusively the LPA 1 receptor.…”

mentioning

confidence: 99%

LPA modulates monocyte migration directly and via LPA-stimulated endothelial cells

Gustin¹,

Steenbrugge²,

Raes³

2008

American Journal of Physiology-Cell Physiology

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Gustin C, Van Steenbrugge M, Raes M. LPA modulates monocyte migration directly and via LPA-stimulated endothelial cells. Am J Physiol Cell Physiol 295: C905-C914, 2008. First published July 16, 2008 doi:10.1152/ajpcell.00544.2007.-Lysophosphatidic acid (LPA) is a bioactive lysophospholipid ligand present in oxidized low-density lipoprotein. The effects of LPA were investigated, first separately on endothelial cells (EC) and monocytes. Using Ki16425 (an LPA1 and LPA3 receptor antagonist), GW9662 [a peroxisome proliferator-activator receptor (PPAR␥) antagonist], and pertussis toxin (that inhibits G i/o), we demonstrate that LPA enhances IL-8 and monocyte chemoattractant protein-1 expression through a LPA1-, LPA3-, Gi/o-and PPAR␥-dependent manner in the EAhy926 cells. The effect of LPA on chemokine overexpression was confirmed in human umbilical vein endothelial cells. LPA was able to enhance monocyte migration at concentrations Ͻ1 M and to inhibit their migration at LPA concentrations Ͼ1 M, as demonstrated by using a chemotaxis assay. We then investigated the effects of LPA on the cross-talk between EC and monocytes by evaluating the chemotactic activity in the supernatants of LPA-treated EC. At 1 M LPA, both cell types respond cooperatively, favoring monocyte migration. At higher LPA concentration (25 M), the chemotactic response varies as a function of time. After 4 h, the chemotactic effect of the cytokines secreted by the EC is counteracted by the direct inhibitory effect of LPA on monocytes. For longer periods of time (24 h), we observe a monocyte migration, probably due to lowered concentrations of bioactive LPA, given the induction of lipid phosphate phosphatase-2 in monocytes that may inactivate LPA. These results suggest that LPA activates EC to secrete chemokines that in combination with LPA itself might favor or not favor interactions between endothelium and circulating monocytes. lysophosphatidic acid; endothelial cells; monocytes; chemotaxis LYSOPHOSPHATIDIC ACID (LPA) is a potent bioactive lipid mediator with multiple cellular effects (21) produced by activated platelets or by enzymatic cleavage of membrane phospholipids (3, 12). The concentration of LPA in the serum is estimated at 2 to 20 M, whereas the concentration in plasma is considerably lower (80 nM to 0.7 M) (10). LPA evokes many cellular responses by binding to five specific G protein-coupled receptors (GPCRs) known as LPA 1-5 that have been cloned and shown to be expressed in most mammalian cells and tissues (for a recent review see Ref. 20). Another GPCR (P2Y5) involved in the maintenance of human hair growth has been recently described as a member of a subgroup of LPA receptors, including LPA 4 and LPA 5 (28). Moreover, the McIntyre group (19) has shown that LPA is also a high-affinity ligand for the peroxisome proliferator-activator receptor ␥ (PPAR␥), suggesting the participation of LPA in intracellular signaling and cell regulation.LPA has recently attracted much interest due to its multiple roles in physiological and pathological co...

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“…Many endogenous ligands of PPAR␥ have been identified, such as 15d-PGJ 2 (Forman et al, 1995), 5-S-hydroxyeicosatetraenoic acid (Nagy et al, 1998), polyunsaturated fatty acids , 13-oxooctadecadienoic acid (Bull et al, 2003), 2,4-dienone 13-oxooctadecadienoic acid (Altmann et al, 2007), and components of oxidized low-density lipoprotein, such as 9-hydroxyoctadecadienoic acid and 13-S-hydroxyoctadecadienoic acid (Nagy et al, 1998). Of these ligands, 5-S-hydroxyeicosatetraenoic acid is produced by the action of 15-lipooxygenase on AA, whereas 15d-PGJ 2 is produced by the action of COX-2 on AA.…”

Section: Discussionmentioning

confidence: 99%

15-Deoxy-Δ^12,14-prostaglandin J₂-Glycerol Ester, a Putative Metabolite of 2-Arachidonyl Glycerol, Activates Peroxisome Proliferator Activated Receptor γ

et al. 2011

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2-Arachidonyl glycerol (2-AG) is an endogenous arachidonic acid derivative capable of suppressing interleukin (IL)-2 production by activated T cells. 2-AG-mediated IL-2 suppression is dependent on cyclooxygenase-2 (COX-2) metabolism and peroxisome proliferator activated receptor ␥ (PPAR␥) activation. The objective of the present studies was to examine whether 15-deoxy-⌬ 12,14 -PGJ 2 -glycerol ester (15d-PGJ 2 -G), a putative metabolite of 2-AG, can mimic the actions of 2-AG on IL-2 regulation through PPAR␥ activation. 15d-PGJ 2 -G bound PPAR␥-ligand binding domain in a PPAR␥ competitive binding assay. 15d-PGJ 2 -G treatment activated PPAR␥ in a reporter assay, and PPAR␥ activation was attenuated when a PPAR␥ antagonist, 2-chloro-5-nitro-N-4-pyridinylbenzamide (T0070907), was present. 15d-PGJ 2 -G treatment suppressed IL-2 production by activated Jurkat cells, which was partially attenuated when pretreated with T0070907. Moreover, IL-2 suppression was pronounced when 15d-PGJ 2 -G was present 30 min before or after T-cell activation. Concordant with IL-2 suppression, 15d-PGJ 2 -G treatment decreased nuclear factor of activated T cells (NFAT) transcriptional activity in transiently transfected Jurkat cells. It is noteworthy that T0070907 alone markedly increased NFAT reporter activity, suggesting the existence of endogenous PPAR␥ activation and modulation of NFAT. Because COX-2 metabolism of 2-AG is important for IL-2 suppression, the effect of 2-AG on COX-2 and PPAR␥ mRNA expression was investigated. 2-AG treatment decreased the up-regulation of COX-2 mRNA after T-cell activation, which suggests negative feedback limiting COX-2-mediated metabolism of 2-AG. PPAR␥ mRNA expression was increased upon activation, and 2-AG treatment produced a modest decrease in PPAR␥ mRNA expression. Collectively, our findings suggest that 15d-PGJ 2 -G activates PPAR␥ to decrease NFAT transcriptional activity and IL-2 expression in activated T cells.

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13-Oxo-ODE is an endogenous ligand for PPARγ in human colonic epithelial cells

Cited by 114 publications

References 50 publications

Peroxisome Proliferator-Activated Receptor .GAMMA. Ligands Isolated from Adlay Seed (Coix lacryma-jobi L. var. ma-yuen STAPF.)

Peroxisome Proliferator-Activated Receptor .GAMMA. Ligands Isolated from Adlay Seed (Coix lacryma-jobi L. var. ma-yuen STAPF.)

LPA modulates monocyte migration directly and via LPA-stimulated endothelial cells

15-Deoxy-Δ^12,14-prostaglandin J₂-Glycerol Ester, a Putative Metabolite of 2-Arachidonyl Glycerol, Activates Peroxisome Proliferator Activated Receptor γ

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13-Oxo-ODE is an endogenous ligand for PPARγ in human colonic epithelial cells

Cited by 114 publications

References 50 publications

Peroxisome Proliferator-Activated Receptor .GAMMA. Ligands Isolated from Adlay Seed (Coix lacryma-jobi L. var. ma-yuen STAPF.)

Peroxisome Proliferator-Activated Receptor .GAMMA. Ligands Isolated from Adlay Seed (Coix lacryma-jobi L. var. ma-yuen STAPF.)

LPA modulates monocyte migration directly and via LPA-stimulated endothelial cells

15-Deoxy-Δ12,14-prostaglandin J2-Glycerol Ester, a Putative Metabolite of 2-Arachidonyl Glycerol, Activates Peroxisome Proliferator Activated Receptor γ

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15-Deoxy-Δ^12,14-prostaglandin J₂-Glycerol Ester, a Putative Metabolite of 2-Arachidonyl Glycerol, Activates Peroxisome Proliferator Activated Receptor γ