M Golubska, I Bogacka, K Mierzejewski, Z Gerwel, A Kurzynska
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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.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"76 1","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Peroxisome proliferator-activated receptor beta/delta ligands as modulators of immune response in lipopolysaccharide-stimulated porcine endometrium: insights from an in vitro study.\",\"authors\":\"M Golubska, I Bogacka, K Mierzejewski, Z Gerwel, A Kurzynska\",\"doi\":\"10.26402/jpp.2025.1.08\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. 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引用次数: 0
摘要
生殖器官的炎症严重威胁着人类和动物的生育能力。最近,人们提出过氧化物酶体增殖激活受体(PPAR)配体作为子宫内膜炎症的潜在调节因子的可能作用。本研究的目的是研究PPARβ/δ配体在生理性和脂多糖(LPS)刺激的黄体中期和卵泡期对猪子宫内膜炎症介质-白细胞介素(IL)-1β、IL-6、IL-8、IL-4、IL-10、肿瘤坏死因子α (TNF-α)、白血病抑制因子(LIF)、toll样受体4 (TLR4)和核因子κ b (NF-κ b) mRNA丰度和蛋白质分泌的影响。此外,还考虑了两种实验设置——正在进行的炎症和正在发生的炎症。子宫内膜组织切片在体外与两种选定的PPARβ/δ配体孵育:激动剂L-165,041或拮抗剂GSK 3787,有或没有LPS。实时聚合酶链反应(RT-PCR)检测mRNA丰度,酶联免疫吸附试验(ELISA)检测培养基中蛋白分泌。两种PPARβ/δ配体均增加炎症状态下IL-1β、IL-6和IL-8 mRNA丰度,减少生理状态下IL-4蛋白分泌,主要发生在发情周期的黄体中期。反过来,只有拮抗剂增加TNF-α的表达。对于所有促炎细胞因子- IL-1β, IL-6, IL-8, TNF-α -我们发现激素和炎症状态均显著影响其mRNA水平,而实验设置显著影响IL-1β, IL-6和TNF-α的表达。结果表明,PPARβ/δ配体可调节猪子宫内膜炎症反应相关细胞因子的表达和分泌。PPARβ/δ配体的主要作用发生在发情周期的黄体中期。在lps刺激的炎症过程中,PPARβ/δ配体通过刺激IL-1β、IL-6、IL-8、TNF-α的表达而具有促炎特性。免疫介质表达的变化取决于发情周期的阶段或子宫内膜炎的病程。
Peroxisome proliferator-activated receptor beta/delta ligands as modulators of immune response in lipopolysaccharide-stimulated porcine endometrium: insights from an in vitro study.
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.
期刊介绍:
Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.