Regulation of pulmonary artery inflamation by PPARβ/δ

Noelia Perez Diaz, Lisa Lione, Louise MacKenzie, Victoria Hutter

Research output: Contribution to conferenceAbstractResearch

Abstract

Introduction: The peroxisome proliferator activated receptor beta delta (PPARβ/δ) is a transcription factor ubiquitously expressed, although more highly active in skeletal muscle, arteries and endothelium. Signalling via PPARβ/δ is involved in lipid metabolism, glucose metabolism, insulin sensitivity, inflammation, and cell proliferation; however, there are great discrepancies in the literature about the role of PPARβ/δ and scientists describe anti- and pro-effects on inflammation, cell migration and cell proliferation after the activation of PPARβ/δ.
As nuclear transcription factor, PPARβ/δ can regulate genes by directly binding the DNA forming a heterodimer with RXR (induction), or alternatively can repress other nuclear transcription factors (trans-repression) and thus indirectly regulate a different group of genes (Figure 1). Lately it is emerging the theory that PPARβ/δ has a dual effect in the cell and indeed acts as a molecular switch between induction and trans-repression having both pro- and anti- effects in inflammation.
Understanding how PPARβ/δ switches between induction and trans-repression mode of action is of great interest and may provide new molecular targets for treating a variety of inflammation-dependent diseases, including atherosclerosis, diabetes, and cancer.
We hypothesised that PPARβ/δ acts as a molecular switch between induction and trans-repression and depending on which mechanism is triggered it will have pro- or anti-effects.
Methods: Pulmonary artery rings from rat were dissected and incubated for 24h under different treatments: vehicle, LPS, LPS+GW0742, LPS+GSK3787, LPS+GW0742+GSK3787, where LPS induces inflammation, GW0742 is a PPARβ/δ agonist and GSK3787 is a PPARβ/δ antagonist. The regulation of the inflammation by PPARβ/δ was examined by measuring the production of the inflammatory biomarkers NO by Griess Assay and IL-6 by ELISA. The switch between induction/trans-repression was analysed through qRT-PCR of target genes.
Results: The presence of GW0742 and GSK3787 together shows the greatest anti-inflammatory effects among all the treatments. GW0742 alone triggers the induction and trans-repression mechanisms of action of PPARβ/δ, but the presence of GW0742 and GSK3787 together only triggers the trans-repression mode of action.
Discussion or Conclusions: Taken all together it suggests that the trans-repression mode of action is responsible for the anti-inflammatory effects of LPS-induced inflammation in the pulmonary artery.
Original languageEnglish
Publication statusPublished - Apr 2019
EventUniversity of Hertfordshire, Life and Medical Sciences Conference -
Duration: 10 Apr 2019 → …

Conference

ConferenceUniversity of Hertfordshire, Life and Medical Sciences Conference
Period10/04/19 → …

Fingerprint

PPAR delta
Pulmonary Artery
Inflammation
Transcription Factors
Anti-Inflammatory Agents
Cell Proliferation
Genes
Lipid Metabolism

Cite this

Perez Diaz, N., Lione, L., MacKenzie, L., & Hutter, V. (2019). Regulation of pulmonary artery inflamation by PPARβ/δ. Abstract from University of Hertfordshire, Life and Medical Sciences Conference, .
Perez Diaz, Noelia ; Lione, Lisa ; MacKenzie, Louise ; Hutter, Victoria. / Regulation of pulmonary artery inflamation by PPARβ/δ. Abstract from University of Hertfordshire, Life and Medical Sciences Conference, .
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abstract = "Introduction: The peroxisome proliferator activated receptor beta delta (PPARβ/δ) is a transcription factor ubiquitously expressed, although more highly active in skeletal muscle, arteries and endothelium. Signalling via PPARβ/δ is involved in lipid metabolism, glucose metabolism, insulin sensitivity, inflammation, and cell proliferation; however, there are great discrepancies in the literature about the role of PPARβ/δ and scientists describe anti- and pro-effects on inflammation, cell migration and cell proliferation after the activation of PPARβ/δ.As nuclear transcription factor, PPARβ/δ can regulate genes by directly binding the DNA forming a heterodimer with RXR (induction), or alternatively can repress other nuclear transcription factors (trans-repression) and thus indirectly regulate a different group of genes (Figure 1). Lately it is emerging the theory that PPARβ/δ has a dual effect in the cell and indeed acts as a molecular switch between induction and trans-repression having both pro- and anti- effects in inflammation.Understanding how PPARβ/δ switches between induction and trans-repression mode of action is of great interest and may provide new molecular targets for treating a variety of inflammation-dependent diseases, including atherosclerosis, diabetes, and cancer. We hypothesised that PPARβ/δ acts as a molecular switch between induction and trans-repression and depending on which mechanism is triggered it will have pro- or anti-effects.Methods: Pulmonary artery rings from rat were dissected and incubated for 24h under different treatments: vehicle, LPS, LPS+GW0742, LPS+GSK3787, LPS+GW0742+GSK3787, where LPS induces inflammation, GW0742 is a PPARβ/δ agonist and GSK3787 is a PPARβ/δ antagonist. The regulation of the inflammation by PPARβ/δ was examined by measuring the production of the inflammatory biomarkers NO by Griess Assay and IL-6 by ELISA. The switch between induction/trans-repression was analysed through qRT-PCR of target genes.Results: The presence of GW0742 and GSK3787 together shows the greatest anti-inflammatory effects among all the treatments. GW0742 alone triggers the induction and trans-repression mechanisms of action of PPARβ/δ, but the presence of GW0742 and GSK3787 together only triggers the trans-repression mode of action.Discussion or Conclusions: Taken all together it suggests that the trans-repression mode of action is responsible for the anti-inflammatory effects of LPS-induced inflammation in the pulmonary artery.",
author = "{Perez Diaz}, Noelia and Lisa Lione and Louise MacKenzie and Victoria Hutter",
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Perez Diaz, N, Lione, L, MacKenzie, L & Hutter, V 2019, 'Regulation of pulmonary artery inflamation by PPARβ/δ' University of Hertfordshire, Life and Medical Sciences Conference, 10/04/19, .

Regulation of pulmonary artery inflamation by PPARβ/δ. / Perez Diaz, Noelia; Lione, Lisa; MacKenzie, Louise; Hutter, Victoria.

2019. Abstract from University of Hertfordshire, Life and Medical Sciences Conference, .

Research output: Contribution to conferenceAbstractResearch

TY - CONF

T1 - Regulation of pulmonary artery inflamation by PPARβ/δ

AU - Perez Diaz, Noelia

AU - Lione, Lisa

AU - MacKenzie, Louise

AU - Hutter, Victoria

PY - 2019/4

Y1 - 2019/4

N2 - Introduction: The peroxisome proliferator activated receptor beta delta (PPARβ/δ) is a transcription factor ubiquitously expressed, although more highly active in skeletal muscle, arteries and endothelium. Signalling via PPARβ/δ is involved in lipid metabolism, glucose metabolism, insulin sensitivity, inflammation, and cell proliferation; however, there are great discrepancies in the literature about the role of PPARβ/δ and scientists describe anti- and pro-effects on inflammation, cell migration and cell proliferation after the activation of PPARβ/δ.As nuclear transcription factor, PPARβ/δ can regulate genes by directly binding the DNA forming a heterodimer with RXR (induction), or alternatively can repress other nuclear transcription factors (trans-repression) and thus indirectly regulate a different group of genes (Figure 1). Lately it is emerging the theory that PPARβ/δ has a dual effect in the cell and indeed acts as a molecular switch between induction and trans-repression having both pro- and anti- effects in inflammation.Understanding how PPARβ/δ switches between induction and trans-repression mode of action is of great interest and may provide new molecular targets for treating a variety of inflammation-dependent diseases, including atherosclerosis, diabetes, and cancer. We hypothesised that PPARβ/δ acts as a molecular switch between induction and trans-repression and depending on which mechanism is triggered it will have pro- or anti-effects.Methods: Pulmonary artery rings from rat were dissected and incubated for 24h under different treatments: vehicle, LPS, LPS+GW0742, LPS+GSK3787, LPS+GW0742+GSK3787, where LPS induces inflammation, GW0742 is a PPARβ/δ agonist and GSK3787 is a PPARβ/δ antagonist. The regulation of the inflammation by PPARβ/δ was examined by measuring the production of the inflammatory biomarkers NO by Griess Assay and IL-6 by ELISA. The switch between induction/trans-repression was analysed through qRT-PCR of target genes.Results: The presence of GW0742 and GSK3787 together shows the greatest anti-inflammatory effects among all the treatments. GW0742 alone triggers the induction and trans-repression mechanisms of action of PPARβ/δ, but the presence of GW0742 and GSK3787 together only triggers the trans-repression mode of action.Discussion or Conclusions: Taken all together it suggests that the trans-repression mode of action is responsible for the anti-inflammatory effects of LPS-induced inflammation in the pulmonary artery.

AB - Introduction: The peroxisome proliferator activated receptor beta delta (PPARβ/δ) is a transcription factor ubiquitously expressed, although more highly active in skeletal muscle, arteries and endothelium. Signalling via PPARβ/δ is involved in lipid metabolism, glucose metabolism, insulin sensitivity, inflammation, and cell proliferation; however, there are great discrepancies in the literature about the role of PPARβ/δ and scientists describe anti- and pro-effects on inflammation, cell migration and cell proliferation after the activation of PPARβ/δ.As nuclear transcription factor, PPARβ/δ can regulate genes by directly binding the DNA forming a heterodimer with RXR (induction), or alternatively can repress other nuclear transcription factors (trans-repression) and thus indirectly regulate a different group of genes (Figure 1). Lately it is emerging the theory that PPARβ/δ has a dual effect in the cell and indeed acts as a molecular switch between induction and trans-repression having both pro- and anti- effects in inflammation.Understanding how PPARβ/δ switches between induction and trans-repression mode of action is of great interest and may provide new molecular targets for treating a variety of inflammation-dependent diseases, including atherosclerosis, diabetes, and cancer. We hypothesised that PPARβ/δ acts as a molecular switch between induction and trans-repression and depending on which mechanism is triggered it will have pro- or anti-effects.Methods: Pulmonary artery rings from rat were dissected and incubated for 24h under different treatments: vehicle, LPS, LPS+GW0742, LPS+GSK3787, LPS+GW0742+GSK3787, where LPS induces inflammation, GW0742 is a PPARβ/δ agonist and GSK3787 is a PPARβ/δ antagonist. The regulation of the inflammation by PPARβ/δ was examined by measuring the production of the inflammatory biomarkers NO by Griess Assay and IL-6 by ELISA. The switch between induction/trans-repression was analysed through qRT-PCR of target genes.Results: The presence of GW0742 and GSK3787 together shows the greatest anti-inflammatory effects among all the treatments. GW0742 alone triggers the induction and trans-repression mechanisms of action of PPARβ/δ, but the presence of GW0742 and GSK3787 together only triggers the trans-repression mode of action.Discussion or Conclusions: Taken all together it suggests that the trans-repression mode of action is responsible for the anti-inflammatory effects of LPS-induced inflammation in the pulmonary artery.

M3 - Abstract

ER -

Perez Diaz N, Lione L, MacKenzie L, Hutter V. Regulation of pulmonary artery inflamation by PPARβ/δ. 2019. Abstract from University of Hertfordshire, Life and Medical Sciences Conference, .