scholarly journals Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis

Reproduction ◽  
2015 ◽  
Vol 150 (5) ◽  
pp. 437-448 ◽  
Author(s):  
Florencia Figueroa ◽  
Alicia Motta ◽  
Mariano Acosta ◽  
Fabian Mohamed ◽  
Liliana Oliveros ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Polycystic Ovary ◽  
Ovarian Response ◽  
Reproductive Age ◽  
Estradiol Valerate ◽  
Tunel Staining ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Nitric Oxide Release ◽  
Factor Α

Polycystic ovarian syndrome is the most common endocrine disorder among women of reproductive age. Little is known about its etiology, although the evidence suggests an intrinsic ovarian abnormality in which endocrine, metabolic, neural and immune factors would be involved. In this work, the effects of macrophage (MO) secretion on ovarian apoptosis in a polycystic ovary syndrome rat model (PCO rat) induced by estradiol valerate are studied. Spleen MO secretions were used to stimulate ovaries and ovarian interstitial and granulosa cells from both PCO and control rats. Ovarian hormones and prostaglandin E2(PGE2) were measured by RIA; ovarian mRNA levels of Bax, Bcl2 and NFkB by RT-PCR; and ovarian inducible nitric oxide synthase (iNOS) by western blot. The number of apoptotic cells was evaluated by TUNEL. In the PCO ovary, the MO secretions from PCO rats increased the Bax and NFkB mRNA expressions and increased TUNEL staining in both granulosa and theca cells. In addition, the PCO MO secretions produced a decrease of nitric oxide release, iNOS protein level and PGE2content in the PCO ovary, and it also induced an increase of androstenedione production by PCO interstitial cells, in comparison with control MO secretions. Considering these results and knowing that testosterone stimulates tumour necrosis factor-α production by PCO MO modifying ovarian response by increasing androstenedione, it is reasonable to suggest that the increase of androgens stimulated in ovarian cells by PCO MO secretions could in turn stimulate the cytokine production from MO, thus maintaining an apoptotic vicious cycle in the PCO ovary.

scholarly journals Modulation of macrophage activation by prostaglandins

1996 ◽  
Vol 5 (1) ◽  
pp. 14-17 ◽  
Author(s):  
L. Sautebin ◽  
R. Carnuccio ◽  
F. D'Acquisto ◽  
M. Di Rosa
Keyword(s):  
Nitric Oxide ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Tumour Necrosis Factor Α ◽  
Nitric Oxide Release ◽  
Factor Α ◽  
Necrosis Factor

The effect of prostaglandtn E2, iloprost and cAMP on both nitric oxide and tumour necrosis factor-α release in J774 macrophages has been studied. Both prostaglandin E2and iloprost inhibited, in a concentration-dependent fashion, the lipopolysaccharide-induced generation of nitric oxide and tumour necrosis factor-α. The inhibitory effect of these prostanoids seems to be mediated by an increase of the second messenger cAMP since it was mimicked by dibutyryl cAMP and potentiated by the selective type IV phosphodiesterase inhibitor RO-20-1724. Our results suggest that the inhibition of nitric oxide release by prostaglandin E2and iloprost in lipopolysaccharide-activated J774 macrophages may be secondary to the inhibition of tumour necrosis factor-α generation, which in turn is likely to be mediated by cAMP.

scholarly journals Sympathetic innervation regulates macrophage activity in rats with polycystic ovary

2018 ◽  
Vol 238 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Florencia Figueroa ◽  
Gisela Mendoza ◽  
Darío Cardozo ◽  
Fabián Mohamed ◽  
Liliana Oliveros ◽  
...  
Keyword(s):  
Culture Media ◽  
Polycystic Ovary ◽  
Sympathetic Innervation ◽  
Endocrine Function ◽  
Estradiol Valerate ◽  
Tunel Staining ◽  
Low Grade ◽  
Mrna Levels ◽  
Adult Rats

Polycystic ovarian syndrome (PCOS) is a low-grade inflammatory disease characterized by hyperandrogenism and ovarian hyperinnervation. The aim of this work is to investigate whether in vivo bilateral superior ovarian nerve (SON) section in adult rats with estradiol valerate-induced PCOS (PCO rats) affects macrophage spleen cells (MФ) and modifies the steroidogenic ability of their secretions. Culture media of MФ from PCO rats and PCO rats with SON section (PCO-SON rats) were used to stimulate in vitro intact ovaries. Compared with macrophages PCO, macrophages from PCO-SON rats released less tumor necrosis factor-α and nitric oxide, expressed lower Bax and Nfkb mRNA and showed reduced TUNEL staining. Also, in PCO rats, the SON section decreased kisspeptin and nerve growth factor mRNA expressions, without changes in Trka receptor mRNA levels. Macrophage secretions from PCO-SON rats decreased androstenedione and stimulated progesterone release in PCO ovaries, compared to macrophage secretions from PCO rats. No changes were observed in ovarian estradiol response. These findings emphasize the importance of the SON in spleen MΦ, since its manipulation leads to secondary modifications of immunological and neural mediators, which might influence ovarian steroidogenesis. In PCO ovaries, the reduction of androstenedione and the improvement of progesterone release induced by PCO-SON MΦ secretion, might be beneficial considering the hormonal anomalies characteristic of PCOS. We present functional evidence that modulation of the immune-endocrine function by peripheral sympathetic nervous system might have implications for understanding the pathophysiology of PCOS.

scholarly journals Oleifolioside A, a New Active Compound, Attenuates LPS-Stimulated iNOS and COX-2 Expression through the Downregulation of NF-κB and MAPK Activities in RAW 264.7 Macrophages

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hai Yang Yu ◽  
Kyoung-Sook Kim ◽  
Young-Choon Lee ◽  
Hyung-In Moon ◽  
Jai-Heon Lee
Keyword(s):  
Nitric Oxide ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Prostaglandin E ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Raw 264.7 Macrophages ◽  
Dendropanax Morbifera ◽  
Cox 2

Oleifolioside A, a new triterpenoid compound isolated fromDendropanax morbiferaLeveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E2(PGE2) production in RAW 264.7 macrophages. Consistent with these findings, oleifolioside A was further shown to suppress the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) in a dose-dependent manner at both the protein and mRNA levels and to significantly inhibit the DNA-binding activity and transcriptional activity of NF-κB in response to LPS. These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-αand subsequent translocation of the NF-κB p65 subunit to the nucleus. Inhibition of NF-κB activation by oleifolioside A was also shown to be mediated through the prevention of p38 MAPK and ERK1/2 phosphorylation. Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.

scholarly journals Simultaneous alterations in ovaries and bone as a result of Polycystic Ovary Syndrome

2021 ◽  
Vol 3 (2) ◽  
pp. 2-14
Author(s):  
Ana Lúcia de Oliveira Bonfá ◽  
Eduardo Donato Alves ◽  
Víctor Fabrício ◽  
Keico Okino Nonaka ◽  
Janete Aparecida Anselmo-Franci ◽  
...  
Keyword(s):  
Cell Culture ◽  
Animal Model ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Estradiol Valerate ◽  
Endocrine Disorders ◽  
Ovary Syndrome ◽  
Bone Properties ◽  
In Vivo Animal Model

Polycystic ovary syndrome (PCOS) is one of the most widely recognized endocrine disorders affecting reproductive-age women. The etiopathogenesis and mechanisms of this syndrome remain unclear. Diagnosis requires two of the following: polycystic ovaries, oligo- or anovulation, and hyperandrogenism. Most women with PCOS display conditions such as metabolic abnormalities, diabetes, obesity, cardiovascular disease, and/or bone dysfunction. Considering the ethical limitations of human studies, animal and cell culture models that reflect some features of PCOS are important for investigation of this syndrome. The aim of the present work was to study some of the endocrine relationships between ovaries and bone tissue in a polycystic ovary syndrome animal model. The study was performed using an estradiol valerate PCOS-induced rat model (n = 30) and bone mesenchymal stem cell cultured from bone marrow of those animals. It was hypothesized that changes of the endocrine relationship between ovaries and bones could be observed in from in vivo animal model and in vitro cell culture assays. The ovarian morphological and endocrine changes seem to be correlated with endocrine, biophysical, and biomechanical changes in bone properties. Mesenchymal stem cells obtained from PCOS-induced rats, cultured for up to 21 days and differentiated into osteoblasts, presented lower viability and reduced mineralization of the extracellular matrix. Taken together, these results indicate important endocrine and structural effects of PCOS in ovaries and bones, contributing to part of the understanding of the pathophysiological mechanisms of PCOS.

scholarly journals Alimentary induced fatty liver and adjuvant therapy with effective natural bioactive molecules

2011 ◽  
Vol 152 (26) ◽  
pp. 1035-1042 ◽  
Author(s):  
Viktor Hegedüs ◽  
Domokos Gerő ◽  
Zoltán Mihály ◽  
Attila Szijártó ◽  
Tivadar Zelles ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fatty Liver ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Redox Homeostasis ◽  
Mrna Levels ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide

Changes of redox-homeostasis generate cytokines, and free radicals influence many intracellular signaling pathways in different liver diseases. Liophylised table beet and carrot powder (GPS Powder Kft. 1361/004/2003BFÁÉÉÁ) containing bioactive components such as betaine, betanins, betaxanthins, flavonoids, polyphenols, glutamine, beta carotene, vitamins and folic acid may produce changes various cellular pathways. Aim: The aim of this study was to determine the protecting effects of bioactive agents of the liophylised table beet and carrot powder on fatty liver in a “short term” experiment. Method: Male Wistar rats were fed with chow with or without high fat (2% cholesterol, 0.5% cholic acid, 20% sunflower oil) and treated with 0.1 or 1 g/bwkg/day natural product for ten days parallel with the feedings. Cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels were determined using molecular biologic methods. Free radicals, H-donating activity, reducing power and free SH-group concentrations were determined by luminometry and spectrophotometry. Mobilized methyl groups were assayed by over pressure liquid chromatography method in liver homogenates. Results: It was found that the higher dose of the natural product better decreased the induced free radical reactions, cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA-levels both in normal and fatty liver tissues. Although treatments failed to exert significant changes in all global antioxidant parameters, mobilized methyl group concentrations were higher after treatments in fatty liver. Favorable tendencies were also noted in the redox-homeostasis of the fatty liver after treatment. Conclusions: As expected, lyophylised table beet and carrot proved to be a “functional food” in rats with alimentary fat induced fatty liver. It cannot be ruled out that this beneficial effect may have clinical relevance. Orv. Hetil., 2011, 152, 1035–1042.

scholarly journals INFLUENCE OF CYTOKINES PRODUCTION, NITROGEN OXIDE METABOLITES AND LIPIDS EXCHANGE ON THE FORMATION OF EXTERNAL GENITAL ENDOMETRIOSIS STAGES IN PATIENTS OF REPRODUCTIVE AGE

2020 ◽  
Vol 17 (35) ◽  
pp. 813-824
Author(s):  
Natalya Victorovna ERMOLOVA ◽  
Yuriy Alekseevich PETROV ◽  
Marina Arkadevna LEVKOVICH ◽  
Ludmila Valerievna KOLESNIKOVA ◽  
Nina Aleksandrovna DRUKKER
Keyword(s):  
Nitric Oxide ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Young Patients ◽  
Reproductive Function ◽  
Transforming Growth Factor Β1 ◽  
Biologically Active ◽  
Reproductive Age ◽  
Nitric Oxide Metabolites ◽  
Factor Α

The relevance of the study is due to the prevalence and increase in the incidence of endometriosis, especially in young patients, its influence on reproductive function, and the lack of reliable non-invasive diagnosis of the disease and its stages. There are no unified views on the etiology and multifactorial pathogenesis of this disease. This article is aimed at revealing the mechanisms of the formation of endometriosis stages basing on the study of the effect of cytokines production, nitric oxide metabolites and lipid metabolism. The main approach to study this problem is both to investigate systemic (blood serum) and local (peritoneal fluid) levels, their comparison. This allows comprehensive consideration of the pathogenesis of the disease and determination of the value of the mentioned biologically active factors depending on the stages of the disease. The article presents new data on the content of high- and low-density lipoproteins, cholesterol, transforming growth factor β1 and tumor necrosis factor α, the content of nitric oxide metabolites and their clinical interpretation is given according to the stages of the disease. The materials of the article are of practical value for researchers of endometriosis and practicing obstetrician-gynecologists.. Keywords: external genital endometriosis, lipoproteins, nitric oxide, transforming growth factor.

scholarly journals Inhibition of Neuroinflammation in LPS-Activated Microglia by Cryptolepine

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Olumayokun A. Olajide ◽  
Harsharan S. Bhatia ◽  
Antonio C. P. de Oliveira ◽  
Colin W. Wright ◽  
Bernd L. Fiebich
Keyword(s):  
Nitric Oxide ◽  
Microglial Activation ◽  
Nuclear Translocation ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Microglia Cell ◽  
Proinflammatory Mediators ◽  
Mitogen Activated Protein ◽  
Cox 2

Cryptolepine, an indoloquinoline alkaloid inCryptolepis sanguinolenta, has anti-inflammatory property. In this study, we aimed to evaluate the effects of cryptolepine on lipopolysaccharide (LPS)- induced neuroinflammation in rat microglia and its potential mechanisms. Microglial activation was induced by stimulation with LPS, and the effects of cryptolepine pretreatment on microglial activation and production of proinflammatory mediators, PGE2/COX-2, microsomal prostaglandin E2synthase and nitric oxide/iNOS were investigated. We further elucidated the role of Nuclear Factor-kappa B (NF-κB) and the mitogen-activated protein kinases in the antiinflammatory actions of cryptolepine in LPS-stimulated microglia. Our results showed that cryptolepine significantly inhibited LPS-induced production of tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1beta (IL-1β), nitric oxide, and PGE2. Protein and mRNA levels of COX-2 and iNOS were also attenuated by cryptolepine. Further experiments on intracellular signalling mechanisms show that IκB-independent inhibition of NF-κB nuclear translocation contributes to the anti-neuroinflammatory actions of cryptolepine. Results also show that cryptolepine inhibited LPS-induced p38 and MAPKAPK2 phosphorylation in the microglia. Cell viability experiments revealed that cryptolepine (2.5 and 5 μM) did not produce cytotoxicity in microglia. Taken together, our results suggest that cryptolepine inhibits LPS-induced microglial inflammation by partial targeting of NF-κB signalling and attenuation of p38/MAPKAPK2.

scholarly journals Pregnancy Protects Hyperandrogenemic Female Rats From Postmenopausal Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 943-952
Author(s):  
Noha M. Shawky ◽  
Chetan N. Patil ◽  
Carolina Dalmasso ◽  
Rodrigo O. Maranon ◽  
Damian G. Romero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Female Rats ◽  
Ovary Syndrome ◽  
Uncomplicated Pregnancy ◽  
Age Related ◽  
Endothelin B

Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.

Regulation of human airway mucins by acrolein and inflammatory mediators

1999 ◽  
Vol 276 (4) ◽  
pp. L549-L555 ◽  
Author(s):  
Michael T. Borchers ◽  
Michael P. Carty ◽  
George D. Leikauf
Keyword(s):  
Inflammatory Mediators ◽  
Control Level ◽  
Carcinoma Cells ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Major Mechanism ◽  
Lung Carcinoma Cells ◽  
Tnf Α ◽  
Human Lung Carcinoma ◽  
Factor Α

Bronchitis, asthma, and cystic fibrosis, marked by inflammation and mucus hypersecretion, can be caused or exacerbated by airway pathogens or irritants including acrolein, an aldehyde present in tobacco smoke. To determine whether acrolein and inflammatory mediators alter mucin gene expression, steady-state mRNA levels of two airway mucins, MUC5AC and MUC5B, were measured (by RT-PCR) in human lung carcinoma cells (NCI-H292). MUC5AC mRNA levels increased after ≥0.01 nM acrolein, 10 μM prostaglandin E2 or 15-hydroxyeicosatetraenoic acid, 1.0 nM tumor necrosis factor-α (TNF-α), or 10 nM phorbol 12-myristate 13-acetate (a protein kinase C activator). In contrast, MUC5B mRNA levels, although easily detected, were unaffected by these agonists, suggesting that irritants and associated inflammatory mediators increase mucin biosynthesis by inducing MUC5ACmessage levels, whereas MUC5B is constitutively expressed. When transcription was inhibited, TNF-α exposure increased MUC5AC message half-life compared with control level, suggesting that transcript stabilization is a major mechanism controlling increased MUC5AC message levels. Together, these findings imply that irritants like acrolein can directly and indirectly (via inflammatory mediators) increase airway mucin transcripts in epithelial cells.

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