Peroxisome proliferator-activated receptor beta/delta ligands as modulators of immune response in lipopolysaccharide-stimulated porcine endometrium: insights from an in vitro study.

Article

作者: Bogacka, I ; Mierzejewski, K ; Gerwel, Z ; Golubska, M ; Kurzynska, A

Inflammation in the reproductive organs is a serious threat to human and animal fertility. Recently, the possible role of peroxisome proliferator-activated receptor (PPAR) ligands as potential regulators of endometrial inflammation has been proposed. The aim of the present study was to investigate the effect of PPARβ/δ ligands on mRNA abundance and protein secretion of selected inflammatory mediators - interleukin (IL)-1β, IL-6, IL-8, IL-4, IL-10, tumor necrosis factor alpha (TNF-α), leukemia inhibitory factor (LIF), toll-like receptor 4 (TLR4) and nuclear factor kappaB (NF-κB) - in porcine endometrium during physiology and lipopolysaccharide (LPS)-stimulated inflammation in both the mid-luteal and follicular phases of the estrous cycle. In addition, two experimental setups - an ongoing and a developing inflammation - were considered. Sections of endometrial tissue were incubated in vitro with two selected PPARβ/δ ligands: agonist L-165,041 or antagonist GSK 3787 with or without LPS. The mRNA abundance was determined by real time polymerase chain reaction (RT-PCR) and protein secretion in the culture medium by enzyme-linked immunosorbent assay (ELISA). Both PPARβ/δ ligands increased the mRNA abundance of IL-1β, IL-6 and IL-8 in the inflammatory state and decreased IL-4 protein secretion in the physiological state, mainly in the mid-luteal phase of the estrous cycle. In turn, only the antagonist increased TNF-α expression. For all proinflammatory cytokines - IL-1β, IL-6, IL-8, TNF-α - we found that both hormonal and inflammatory status significantly influenced their mRNA levels, while the experimental setup notably affected the expression of IL-1β, IL-6 and TNF-α. The results show that PPARβ/δ ligands modulate the expression and secretion of cytokines involved in the inflammatory response in the porcine endometrium. The main effect of PPARβ/δ ligands was noted during the mid-luteal phase of the estrous cycle. During LPS-stimulated inflammation, PPARβ/δ ligands appear to have pro-inflammatory properties by stimulating the expression of IL-1β, IL-6, IL-8, TNF-α. The changes in the expression of immune mediators depend on the phase of the estrous cycle or the course of endometritis.

2025-02-01·Journal of Neurochemistry

PPARβ/δ Activation Improves Corticosterone‐Induced Oxidative Stress Damage in Astrocytes by Targeting UBR5/ATM Signaling

Article

作者: Chen, Ye‐Fan ; Cai, Zhen‐Yu ; Sun, Xiu‐Lan ; Dong, Yin‐Feng ; Ren, Xue‐Wei ; Hong, Chen ; Xu, Hang ; Ji, Juan

ABSTRACTOxidative stress‐mediated astrocytic damage contributes to nerve injury and the development of depression, especially under stress conditions. Peroxisomes and pexophagy are essential for balancing oxidative stress and protein degradation products. Our previous findings suggest that peroxisome proliferators‐activated receptor β/δ (PPARβ/δ) activation significantly alleviates depressive behaviors by preventing astrocytic injury. However, the underlying mechanisms remain unclear. In the present study, we established oxidative injury by treating astrocytes with corticosterone. Subsequently, PPARβ/δ agonists and antagonists were applied to determine the effects of PPARβ/δ on balancing peroxisomes and pexophagy in astrocytes. The PPARβ/δ agonist (GW0742) significantly improved cell viability and decreased intracellular reactive oxygen species (ROS) production induced by corticosterone, while pretreatment with the PPARβ/δ, antagonist GSK3787 reversed the effects of GW0742. Moreover, activating PPARβ/δ promoted peroxisomal biogenesis factor 5 (PEX5)‐mediated pexophagy by enhancing the phosphorylation of ataxia‐telangiectasia mutated (ATM) kinase. Conversely, blocking PPARβ/δ with GSK3787 partially abolished the effects of GW0742. Further investigations demonstrated that activation of PPARβ/δ not only induced transcription of the ubiquitin protein ligase E3 component n‐recognin 5 (UBR5) but also enhanced the interaction between PPARβ/δ and UBR5, contributing to ATM interactor (ATMIN) degradation, and increased phosphorylated ATM kinase levels. Therefore, this study revealed that activating PPARβ/δ improves corticosterone‐induced oxidative damage in astrocytes by enhancing pexophagy. PPARβ/δ directly interacts with UBR5 to facilitate ATMIN degradation and promotes ATM phosphorylation, thereby maintaining the balance between peroxisomes and pexophagy. These findings suggest that PPARβ/δ is a potential target for promoting pexophagy in astrocytes upon stress.

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2024-09-01·Theriogenology

PPAR beta/delta regulates the immune response mechanisms in the porcine endometrium during LPS-induced inflammation – An in vitro study

Article

作者: Bogacka, Iwona ; Gerwel, Zuzanna ; Mierzejewski, Karol ; Golubska, Monika ; Paukszto, Łukasz ; Kurzyńska, Aleksandra

Inflammation in the reproductive tract has become a serious threat to animal fertility. Recently, the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the context of reproduction and the inflammatory response has been highlighted, but the role of PPARβ/δ has not been fully elucidated. The aim of the present study was to investigate the in vitro effect of PPARβ/δ ligands (agonist: L-165,041 and antagonist: GSK 3787) on the transcriptome profile of porcine endometrium during LPS-induced inflammation in the mid-luteal and follicular phases of the oestrous cycle (days 10-12 and 18-20, respectively) using the RNA-Seq method. During the mid-luteal phase of the oestrous cycle, the current study identified 145 and 143 differentially expressed genes (DEGs) after treatment with an agonist or antagonist, respectively. During the follicular phase of the oestrous cycle, 55 and 207 DEGs were detected after treatment with an agonist or antagonist, respectively. The detected DEGs are engaged in the regulation of various processes, such as the complement and coagulation cascade, NF-κB signalling pathway, or the pathway of 15-eicosatetraenoic acid derivatives synthesis. The results of the current study indicate that PPARβ/δ ligands are involved in the control of the endometrial inflammatory response.

100 项与 GSK3787 相关的药物交易

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