PPARβ/δ ligands regulate the expression of immune response mediators in the porcine endometrium – An in vitro study

Kunicka, Zuzanna; Kurzyńska, Aleksandra; Szydłowska, Anna; Kaczyńska, Beata; Bogacka, Iwona

doi:10.1016/j.theriogenology.2019.05.022

Cited by 11 publications

(9 citation statements)

References 42 publications

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“…Although the direct link of PPARβ/δ to IL-8 is suggestive, some studies have already related the activation of PPARβ/δ with the modulation of expression of IL-8 in endothelial cells and endometrium tissue participating in in ammation [33][34][35]. In line with this evidence, our results suggest that a decrease in the PPARβ/δ expression in leukocytes might consequently augment the IL-8 levels and, thereby, the in ammatory response during obesity.…”

Section: Discussionsupporting

confidence: 83%

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

Vargas-Sánchez¹,

Vargas²,

Urrutia³

et al. 2020

Preprint

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Background Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by obesity directly affects the metabolism of various tissues. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors and transcription factors essential for energy homeostasis of different tissues. Despite its wide-ranging expression and function, the functional mismatch of the PPAR subtypes establish biological mechanisms responsible for metabolic diseases from childhood. In addition, the glucagon-like peptide-1 receptor (GLP-1R) activation can influence insulin secretion, but also the cytokine profile possibly mediated through PPARγ activation. However, to date, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients has been unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R, and its correlation with metabolic, hormonal, inflammatory, and anthropometric markers in an obese pediatric population. Results Obese children and adolescents presented a significant increase in anthropometric and body composition parameters, TG, VLDL, TG/HDL, A/G index, and HOMA score when compared to the control group. Obese participants exhibited a pro-inflammatory profile with an augment of IL-8 (p = 0,0081), IL-6 (p = 0,0005), TNF-α (p = 0,0004), IFN-γ (p = 0,0110), MCP-1 (p = 0,0452), and adipsin (p = 0,0397), whereas displayed a reduction of adiponectin (p = 0,0452). The expression of PPARα and GLP-1R was lower in the leukocytes from obese participants than in lean subjects. Furthermore, PPARα correlates negatively with TNF-α (p = 0,0383), while GLP-1R did not show correlation with any inflammatory variable. However, both receptors correlate negatively with the abdominal skinfold. Although PPARβ/δ expression was similar between groups, it was negatively associated with IL-8 levels (p = 0,0085). Conclusions PPARα and PPARβ/δ expression are negatively associated with the proinflammatory markers TNF-α and IL-8, respectively, suggesting participation in the regulation of inflammation observed in pediatric obesity. Furthermore, PPARα and GLP-1R are downregulated in leukocytes from obese children and adolescents, and both receptors are associated with the abdominal skinfold suggesting a role in fat distribution that could indirectly affect the function of different immune cells and the secreted cytokines. Thereby, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.

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Section: Discussionsupporting

confidence: 83%

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

Vargas-Sánchez¹,

Vargas²,

Urrutia³

et al. 2020

Preprint

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“…Furthermore, the ligands did not change IL‐6 mRNA expression, but the PPARα agonist increased IL‐6 protein expression in the mid‐luteal phase of the estrous cycle and at the beginning of implantation. The absence of any associations between mRNA and protein expression in the current study and in our previous research could be attributed to various biological and technical factors, such as differences in mRNA and protein stability, transcriptional and posttranscriptional regulation, and existing feedback, which can suppress mRNA expression through high protein expression and attenuate post‐transcriptional processes through high mRNA content . Further research is needed to determine biological factors that exert the greatest influence on the relationship between mRNA and protein expression …”

Section: Discussioncontrasting

confidence: 46%

“…The procedures for tissue harvesting and culture were described previously . Briefly, tissue explants (200 ± 10 mg) were incubated in the M199 medium (Sigma Aldrich) supplemented with 0.1% BSA fraction V and antibiotics: nystatin (120 IU/mL; Sigma Aldrich) and gentamicin (40, 40 mg/mL; Sigma Aldrich).…”

Section: Methodsmentioning

confidence: 99%

“…After incubation, endometrial explants were homogenized in ice with a cold isolation buffer (Tris‐HCl [10 mmol/L], EDTA [5 mmol/L], NaCl [50 mmol/L], sodium pyrophosphate [30 mmol/L], sodium fluoride [50 mmol/L], sodium azide [0.02%], sodium orthovanadate [100 µmol/L], Triton X‐100 [1%], phenylmethanesulfonyl fluoride [1 mmol/L], leupeptin [2 µg/mL], aprotinin [2 µg/mL], and pepstatin [1 µg/mL]) according to a previously described procedure . The samples were tested individually in the Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

“…We have found that interferon γ (IFNγ) increases mRNA expression of PPARα in the porcine endometrium during early pregnancy (day 14) . Our recent research has shown that two other isoforms of PPAR—beta and gamma—regulate the mRNA expression and protein secretion of NF‐κB and selected pro‐ and anti‐inflammatory cytokines in the in vitro incubation of porcine endometrial explants during the mid‐ and late‐luteal phases of the estrous cycle as well as during early pregnancy . Taking into account previous reports, we hypothesized that PPARα changes the gene and protein expression of immune response mediators in porcine endometrial explants.…”

Section: Introductionmentioning

confidence: 96%

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Peroxisome proliferator‐activated receptor alpha regulates the expression of the immune response mediators in the porcine endometrium during the estrous cycle and early pregnancy

Kunicka

Kurzyńska

Szydłowska

et al. 2019

American J Rep Immunol

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Problem Cytokines are immune response mediators that play an important role in the regulation of reproductive functions. An association between cytokines and peroxisome proliferator receptors (PPARs) has been reported in various tissues, including the endometrium. The present study aimed to evaluate the impact of PPARα ligands on the expression of nuclear factor kappa B (NF‐κB) and cytokines (interleukin [IL]‐1β, IL‐4, IL‐6, IL‐8, IL‐10, and LIF) in the porcine endometrium in different reproductive stages. Methods of study Endometrial slices were collected from gilts on days 10‐12 or 14‐16 of the estrous cycle and pregnancy. Endometrial tissue explants were incubated in vitro in the presence or absence of PPARα agonist WY‐14643 and antagonist MK886. Expression of mRNA and protein for NF‐ĸB and selected cytokines was evaluated by real‐time PCR and immunoblot. Results PPARα agonist WY‐14643 decreased the mRNA expression of NF‐κB in most of the analyzed stages (excluding days 10‐12 of the estrous cycle), but increased the expression of NF‐κB protein (excluding days 14‐16 of pregnancy). The WY‐14643 increased expression of IL‐1β and IL‐6 proteins, and the mRNA expression of IL‐8 and LIF, decreased IL‐4 expression, and did not affect the mRNA and protein expression of IL‐10. Conclusion The obtained results demonstrate that PPARα is involved in the regulation of NF‐κB and cytokine expression in the porcine endometrium. PPARα ligands exert a varied influence on immune system components, which could be attributed to differences in the receptivity of porcine endometrial tissue during the reproductive cycle.

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PPARγ ligands modulate the immune response mediators in the pig myometrium — An in vitro study

Kurzyńska

Kunicka

Mierzejewski

et al. 2021

Animal Reproduction Science

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PPARβ/δ ligands regulate the expression of immune response mediators in the porcine endometrium – An in vitro study

Cited by 11 publications

References 42 publications

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

PPARα and PPARβ/δ Expression is Associated with Proinflammatory Markers in an Obese Pediatric Population

Peroxisome proliferator‐activated receptor alpha regulates the expression of the immune response mediators in the porcine endometrium during the estrous cycle and early pregnancy

PPARγ ligands modulate the immune response mediators in the pig myometrium — An in vitro study

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