interleukin-8 and Polycystic-Ovary-Syndrome

Elevated serum levels of inflammatory mediators in conditions such as PCOS reflect a low-grade chronic inflammation and this has been attributed to be associated with insulin-resistance in PCOS. Therefore, insulin-sensitizing agents are suggested to improve both reproductive as well as metabolic aspects of PCOS. This study aimed to compare the effects of metformin taken alone with that of a combination of metformin and pioglitazone on menstrual cycle, hormonal parameters, insulin resistance, and inflammatory biomarkers in women with PCOS. One hundred and six women with PCOS participated in the study. All subjects were randomized into two-arm intervention groups (Arm 1 and 2). Participants in Arm-1 received metformin (500 mg BD) daily while those in Arm-2 a combination of metformin (500 mg BD) and pioglitazone (15 mg BD) for 12 wks. Serum levels of IL-6 and IL-8 were measured using ELISA whereas insulin resistance was assessed using HOMA-IR. At baseline women with PCOS had significantly elevated circulating concentrations of IL-6 and IL-8. Treatment decreased IL-6 in both the groups, however, only the combination group showed a significant decrease (p=0.005). Serum IL-8 level had a significant decrease after treatment in both groups (p <0.001). HOMA-IR and insulin levels also decreased in both the groups (both p <0.001). Testosterone, FSH, and prolactin significantly decreased in both groups. LH also decreased in both groups, however, the change was significant only in the combination group (p=0.013). Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.

Topics: Adult; Biomarkers; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Interleukin-6; Interleukin-8; Metformin; Pioglitazone; Polycystic Ovary Syndrome; Prognosis; Young Adult

This research was conducted to assess the effects of coenzyme Q10 (CoQ10) intake on gene expression related to insulin, lipid and inflammation in subjects with polycystic ovary syndrome (PCOS).. This randomized double-blind, placebo-controlled trial was conducted on 40 subjects diagnosed with PCOS. Subjects were randomly allocated into two groups to intake either 100 mg CoQ10 (n = 20) or placebo (n = 20) per day for 12 weeks. Gene expression related to insulin, lipid and inflammation were quantified in blood samples of PCOS women with RT-PCR method.. Results of RT-PCR shown that compared with the placebo, CoQ10 intake downregulated gene expression of oxidized low-density lipoprotein receptor 1 (LDLR) (p < 0.001) and upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p = 0.01) in peripheral blood mononuclear cells of subjects with PCOS. In addition, compared to the placebo group, CoQ10 supplementation downregulated gene expression of interleukin-1 (IL-1) (p = 0.03), interleukin-8 (IL-8) (p = 0.001) and tumor necrosis factor alpha (TNF-α) (p < 0.001) in peripheral blood mononuclear cells of subjects with PCOS.. Overall, CoQ10 intake for 12 weeks in PCOS women significantly improved gene expression of LDLR, PPAR-γ, IL-1, IL-8 and TNF-α.

Topics: Adult; Dietary Supplements; Double-Blind Method; Female; Gene Expression; Gene Expression Regulation; Humans; Inflammation; Insulin; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Lipid Metabolism; Polycystic Ovary Syndrome; PPAR gamma; Receptors, Oxidized LDL; Tumor Necrosis Factor-alpha; Ubiquinone

The aim of this study was to evaluate the effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome (PCOS).. Forty PCOS women were allocated into two groups and treated with 1000mg omega-3 fatty acids plus 400 IU vitamin E supplements (n = 20) or placebo (n = 20) per day for 12 weeks. Parameters of mental health were recorded at baseline and after the 12-week intervention. Gene expression related to insulin and inflammation were measured in blood samples of PCOS women.. After the 12-week intervention, compared with the placebo, omega-3 and vitamin E co-supplementation led to significant improvements in beck depression inventory total score (- 2.2 ± 2.0 vs. - 0.2 ± 1.3, P = 0.001), general health questionnaire scores (- 5.5 ± 4.6 vs. - 1.0 ± 2.3, P < 0.001) and depression anxiety and stress scale scores (- 7.2 ± 5.2 vs. - 1.3 ± 1.3, P < 0.001). Compared with the placebo, omega-3 and vitamin E co-supplementation could up-regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) expression (P = 0.04) in peripheral blood mononuclear cells (PBMC) of PCOS women. In addition, compared with the placebo, omega-3 and vitamin E co-supplementation down-regulated interleukin-8 (IL-8) (P = 0.003) and tumor necrosis factor alpha (TNF-α) expression (P = 0.001) in PBMC of PCOS women. There were no significant difference between-group changes in glucose transporter 1 (GLUT-1), IL-6 and transforming growth factor beta (TGF-β) in PBMC of PCOS women.. Omega-3 and vitamin E co-supplementation was effective in improving parameters of mental health, and gene expression of PPAR-γ, IL-8 and TNF-α of women with PCOS.

Topics: Adult; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Gene Expression; Humans; Inflammation; Insulin; Interleukin-8; Leukocytes, Mononuclear; Polycystic Ovary Syndrome; PPAR gamma; Treatment Outcome; Tumor Necrosis Factor-alpha; Vitamin E; Vitamins

This study was conducted to determine the effects of fish oil administration on gene expression related to insulin, lipid and inflammation in women with polycystic ovary syndrome (PCOS).. This randomized, double-blind, placebo-controlled trial was conducted among 40 subjects with PCOS, aged 18-40 years. Subjects were randomly allocated into two groups to take either 1000 mg omega-3 fatty acids from fish oil (n = 20) or placebo (n = 20) twice a day for 12 weeks. Gene expression related to insulin, lipid and inflammation was quantified in peripheral blood mononuclear cells (PBMC) of PCOS women with RT-PCR method.. Our study demonstrated that after the 12-week intervention, compared with the placebo, fish oil supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < .001) in PBMC of subjects with PCOS. In addition, compared to the placebo, taking fish oil supplements downregulated gene expression of interleukin-1 (IL-1) (P = .02) and interleukin-8 (IL-8) (P = .01) in PBMC of subjects with PCOS. We did not observe any significant effect of fish oil supplementation on gene expression of lipoprotein(a) [LP(a)], low-density lipoprotein receptor (LDLR), glucose transporter 1 (GLUT-1), tumour necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) in PBMC of subjects with PCOS.. Overall, fish oil supplementation for 12 weeks to subjects with PCOS significantly improved gene expression of PPAR-γ, IL-1 and IL-8, but did not influence gene expression of LP(a), LDLR, GLUT-1, TNF-α and TGF-β.

Topics: Adolescent; Adult; Double-Blind Method; Drug Administration Schedule; Fatty Acids, Omega-3; Female; Fish Oils; Gene Expression; Humans; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Polycystic Ovary Syndrome; PPAR gamma; Up-Regulation; Young Adult

Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk.. To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women.. Randomized, open-labelled parallel study.. Endocrinology outpatient clinic in a referral centre.. Twenty patients with PCOS (PCOS) and biochemical hyperandrogenaemia with a body mass index of ≥30 kg/m. Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks of treatment.. After 12 weeks of rimonabant treatment, there was a significant increase in VEGF (99·2 ± 17·6 vs 116·2 ± 15·8 pg/ml, P < 0·01) and IL-8 (7·4 ± 11·0 vs 18·1 ± 13·2 pg/ml, P < 0·05) but not after metformin (VEGF P = 0·7; IL-8 P = 0·9). There was no significant difference in the pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment.. This study suggests that rimonabant CB-I blockade paradoxically raised VEGF and the cytokine IL-8 in obese women with PCOS that may have offset the potential benefit associated with weight loss.

Topics: Biomarkers; Cannabinoid Receptor Antagonists; Cytokines; Female; Humans; Hyperandrogenism; Inflammation; Interleukin-8; Metformin; Obesity; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Vascular Endothelial Growth Factor A; Weight Loss

Polycystic ovary syndrome (PCOS) is accompanied by chronic inflammation and metabolic disorders. Whether metabolic abnormalities affect inflammation in PCOS or not, the underlying mechanism remains to be clarified.. We aimed to investigate changes in fatty acids and their effects on inflammatory response in the follicular niche of PCOS patients.. This study recruited 50 PCOS patients and 50 age-matched controls for follicular fluids and ovarian mural granulosa cells collection. The human ovarian granulosa cell line KGN was used for evaluating the effect of oleic acid (OA) stimulation. The levels of follicular fatty acids were measured by liquid chromatography-tandem mass spectrometry. The concentrations of inflammatory cytokines were detected by electrochemiluminescence and enzyme-linked immunosorbent assays. The regulation of inflammation-related genes was confirmed by quantitative polymerase chain reaction and Western blotting after OA stimuli.. Three saturated fatty acids and 8 unsaturated fatty acids were significantly elevated in follicular fluids of PCOS patients compared to those in controls. The concentrations of follicular interleukin (IL)-6, IL-8, and mature IL-18 were significantly higher in the PCOS group and were positively correlated with the levels of fatty acids. Moreover, OA stimulation upregulated the transcription levels of IL-6 and IL-8 via extracellularly regulated kinase 1/2 signaling pathways in KGN cells. Furthermore, OA treatment induced reactive oxygen species production and inflammasome activation, which is manifested by enhanced caspase-1 activity and mature IL-18 protein level.. Fatty acid metabolism was significantly altered in the follicular niche of PCOS patients. Elevated levels of fatty acids could induce ovarian inflammation both at the transcriptional level and in posttranslational processing.

Topics: Fatty Acids; Female; Follicular Fluid; Granulosa Cells; Humans; Inflammasomes; Inflammation; Interleukin-18; Interleukin-6; Interleukin-8; MAP Kinase Signaling System; Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is featured as a common endocrine disorder in reproductive-aged women, while its pathophysiology is not fully illustrated. This study examined potential actions of resveratrol in PCOS cellular model and explored the underlying interaction between resveratrol and toll-like receptor 2 (TLR2). This study performed the bioinformatics analysis on two microarray datasets (GSE34526 and GSE138518). We found that TLR2 was one of potential hub genes that may be associated with PCOS. Further examination showed that TLR2 was highly expressed in granulosa cells from PCOS group compared with control. The in vitro studies showed that LPS intervention caused an increased expression of TLR2 and the pro-inflammatory mediators, and induced oxidative stress in the granulosa cells, which was concentration-dependently antagonized by resveratrol treatment. TLR2 silence significantly attenuated LPS-induced increase TNF-α, IL-1β, IL-6 and IL-8 expression and oxidative stress of granulosa cells. Furthermore, TLR2 overexpression promoted inflammatory response and oxidative stress in the granulosa cells, which was antagonized by resveratrol treatment. In conclusion, resveratrol could attenuate LPS-induced inflammation and oxidative stress in granulosa cells, and the underlying mechanisms may be related to the inhibitory effect of resveratrol on TLR2 expression in granulosa cells.

Topics: Adult; Female; Granulosa Cells; Humans; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharides; Oxidative Stress; Polycystic Ovary Syndrome; Resveratrol; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha

To determine the relationships among alpha1-antitrypsin (A1AT), pro-inflammatory cytokines, neutrophil elastase (NE), interleukin (IL)- 1β, and IL-8 in cases with polycystic ovary syndrome (PCOS).. Female rats in the control group were fed and watered normally. Female rats in the PCOS group were given high-fat diets and letrozole (1% carboxymethyl cellulose' [CMC] solution) CMC by gavage at a dose of l mg/kg body weight daily for 23 days. The mRNA levels of A1AT and NE in rat ovaries were detected by performing real-time polymerase chain reaction (PCR) in the laboratory of Norman Bethune College of Medicine, Jilin University, China in 2017. All serum samples were collected from the Second Hospital of Jilin University from October 2021 to November 2021 for obesity concurrent with PCOS. Molecular docking of A1AT with NE, IL-8, and IL-1β was investigated using the Insight II software ZDOCK tool. This study was carried out at the Reproductive Center, The Second Hospital of Jilin University, Changchun, China from June 2021 to July 2022.. The expression of the A1AT mRNA decreased in the ovary tissues of PCOS rats relative to that of healthy controls, while the expression of NE mRNA increased compared to that of normal controls. The serum A1AT expression in PCOS cases decreased considerably relative to their expression in normal controls. However, the expression of NE, IL-1β, and IL-8 increased significantly relative to their expression in the control (. Alpha1-antitrypsin is closely associated with NE, IL-1β, and IL-8. Therefore, we speculate that A1AT might ameliorate PCOS symptoms by inhibiting pro-inflammatory factors: NE, IL-1β, and IL-8.

Topics: alpha 1-Antitrypsin; Animals; Cytokines; Female; Interleukin-8; Molecular Docking Simulation; Polycystic Ovary Syndrome; Rats; RNA, Messenger

PCOS is the most common endocrinopathy in women; associated with obesity and insulin resistance (IR). IR leads to accumulation of advanced-glycation-end-products (AGEs) and their receptor, RAGE. PCOS patients have increased levels of vascular endothelial growth factor (VEGF), interleukin 6/8 (IL-6/8) and anti-Mϋllerian-hormone (AMH). PEDF is a secreted-glycoprotein known for its anti-angiogenic and anti-inflammatory properties. We aimed to elucidate the role of PEDF in the pathogenesis and treatment of PCOS. We used a prenatal PCOS mouse model and fed the female offspring a high-fat diet, inducing metabolic PCOS (met.PCOS) characteristics. Female offspring were divided into three groups: control; met.PCOS; met.PCOS + recombinant PEDF (rPEDF). Met.PCOS mice gained more weight, had elevated serum IL-6 and higher mRNA levels of AMH, PEDF and RAGE in their granulosa cells (GCs) than met.PCOS + rPEDF mice. An in vitro Met.PCOS model in human GCs (KGN) line was induced by prolonged incubation with insulin/AGEs, causing development of IR. Under the same conditions, we observed an elevation of VEGF, IL-6/8 mRNAs, concomitantly with an increase in PEDF mRNA, intracellular protein levels, and an elevation of PEDF receptors (PEDF-Rs) mRNA and protein. Simultaneously, a reduction in the secretion of PEDF from GCs, was measured in the medium. The addition of rPEDF (5 nM) activated P38 signaling, implying that PEDF-Rs maintained functionality, and negated AGE-induced elevation of IL-6/8 and VEGF mRNAs. Decreased PEDF secretion may be a major contributor to hyperangiogenesis and chronic inflammation, which lie at the core of PCOS pathogenesis. rPEDF treatment may restore physiological angiogenesis inflammatory balance, thus suggesting a potential therapeutic role in PCOS.

Topics: Animals; Disease Models, Animal; Eye Proteins; Female; Humans; Interleukin-6; Interleukin-8; Mice; Nerve Growth Factors; Polycystic Ovary Syndrome; Serpins; Vascular Endothelial Growth Factor A

Chronic low-grade inflammation has been suggested as a key contributor of the pathogenesis and development of polycystic ovary syndrome (PCOS). To investigate the association between oxidative stress status and inflammatory cytokines in follicular fluid of 21 PCOS women compared to 21 women with normal ovarian function who underwent intra-cytoplasmic sperm injection. Concentration of IL-6, IL-8, IL-10, and TNF-α was measured using sandwich ELISA. Oxidative stress was examined by measuring total oxidant status (TOS), malondialdehyde (MDA), total antioxidant capacity (TAC), and thiol groups. PCOS women had an elevated concentration of MDA and TOS compared to controls. Levels of TAC and thiol groups were lower in PCOS compared to controls. PCOS patients had a higher concentration of IL-6, IL-8, and TNF-α compared to controls. Concentration of IL-10 was lower in PCOS compared to controls. Significant correlations were found between MDA and TOS concentration with TNF-α and between IL-6 and MDA, IL-8 and TAC, IL-10 and TOS levels and also between IL-10 and TAC levels. TAC and thiol groups were negatively correlated with TNF-α. Increased oxidative stress in PCOS is associated with inflammation which is closely linked. Inflammation can induce production of inflammatory cytokines in this syndrome and directly stimulates excess ovarian androgen production.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Down-Regulation; Female; Follicular Fluid; Hospitals, University; Humans; Infertility, Female; Interleukin-10; Interleukin-6; Interleukin-8; Iran; Middle Aged; Ovary; Oxidative Stress; Polycystic Ovary Syndrome; Sperm Injections, Intracytoplasmic; Tumor Necrosis Factor-alpha; Up-Regulation

Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity and endometrial cancer.. We hypothesized that an altered endocrine/metabolic environment in PCOS may result in an endometrial "disease phenotype" affecting the gene expression of different endometrial cell populations, including stem cells and their differentiated progeny.. This was a prospective study conducted at an academic medical center.. Proliferative-phase endometrium was obtained from 6 overweight/obese PCOS (National Institutes of Health criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting-isolated endometrial epithelial cells (eEPs), endothelial cells, stromal fibroblasts (eSFs), and mesenchymal stem cells (eMSCs). Gene expression data were validated using microfluidic quantitative RT-PCR and immunohistochemistry.. The comparison between eEP(PCOS) and eEP(Ctrl) showed dysregulation of inflammatory genes and genes with oncogenic potential (CCL2, IL-6, ORM1, TNAIFP6, SFRP4, SPARC). eSF(PCOS) and eSF(Ctrl) showed up-regulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSC(PCOS) vs eMSC(Ctrl), the most up-regulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). Immunohistochemistry scoring showed increased expression of CCL2 in eEP(PCOS) and eSF(PCOS) compared with eEP(Ctrl) and eSF(Ctrl) and IL-6 in eEP(PCOS) compared with eEP(Ctrl).. Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and prooncogenic changes, independent of body mass index, especially in eEP(PCOS) and eMSC(PCOS), compared with controls. The study reveals an endometrial disease phenotype in women with PCOS with potential negative effects on endometrial function and long-term health.

Topics: Adult; Body Mass Index; Cell Proliferation; Endometrium; Female; Gene Expression; Humans; Inflammation; Interleukin-6; Interleukin-8; Mesenchymal Stem Cells; Obesity; Overweight; Polycystic Ovary Syndrome; Up-Regulation