Yazar "Arici, Aydin" seçeneğine göre listele

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    The broad-spectrum chemokine inhibitor NR58-3.14.3 suppresses the implantation and survival of human endometrial implants in the nude mice endometriosis model
    (Springer Heidelberg, 2007) Kayisli, Umit A.; Berkkanoglu, Murat; Zhang, Lufang; Kizilay, Gulnur; Arici, Aydin
    Many chemokines likely contribute to the pathogenesis of endometriosis. The authors hypothesize that the broad-spectrum chemokine inhibitor NR58-3.14.3 may prevent ectopic human endometrium implantation and growth. After placing human endometrium fragments into the peritoneal cavity, ovariectomized athymic nude mice (n = 31) receiving intramuscular estradiol valerate were randomly assigned to daily intraperitoneal injections of either phosphate-buffered saline or NR58-3.14.3. Fourteen days later, the implant number and volume, proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) index, and MTT cell viability were assessed in the implants. NR58-3.14.3 reduced the total number (45%) and total volume (81%) of endometriotic lesions (P < .05) and revealed a lower PCNA and higher TUNEL index in ectopic implants compared with controls (P < .05). NR58-3.14.3 treatment did not affect endometrial cell proliferation in vitro. NR58-3.14.3, by possibly regulating cell survival, can reduce the number and size of ectopic implants in vivo, supporting the potential use of chemokine inhibitors in novel therapies for endometriosis.
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    Differential regulation of Akt phosphorylation in endometriosis
    (Elsevier Sci Ltd, 2009) Cinar, Ozgur; Seval, Yasemin; Uz, Yesim H.; Cakmak, Hakan; Ulukus, Murat; Kayisli, Umit A.; Arici, Aydin
    Protein kinase B (PKB/Akt), a serine/threonine kinase, regulates the function of many cellular proteins involved in apoptosis and proliferation. It was postulated that there is a higher Akt activity in endometriosis compared with normal endometrium, and that oestrogen may be one of the factors responsible for the high Akt activation in endometriotic cells. Phospho-Akt (pAkt) concentrations in normal, eutopic and ectopic endometrial tissues were compared by immunohistochemistry, and a higher pAkt immunoreactivity was revealed in eutopic and ectopic endometrium compared with normal endometrium, in vivo. Higher Akt phosphorylation in stromal cells from eutopic endometrium was observed, when compared with normal, ill vitro (P < 0.05). Akt phosphorylation was rapidly (2-10 min) stimulated when endometrial stromal cells from normal and endometriosis patients were treated with 17 beta-oestradiol. In endometrial stromal cells from the endometriosis group, ICI 182,780 (10, a specific oestrogen receptor antagonist) failed to antagonize the effect of oestradiol when combined with oestradiol, and revealed a stimulatory effect on Akt phosphorylation when given alone (P < 0.05). In Conclusion, since Akt affects cell survival, it is suggested that increased Akt phosphorylation may be related to the altered apoptosis/proliferation harmony in endometriosis, and therefore Akt may play a critical role in the pathogenesis of endometriosis.
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    ERK expression and activity in human myometrium and leiomyoma.
    (Sage Publications Inc, 2008) Altun, Turba; Murk, William; Uz, Yesim H.; Karipcin, Sinent; Kayisli, Umit A.; Arici, Aydin
    [Abstract Not Available]
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    Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro
    (Springer, 2008) Kizilay, Gulnur; Cakmak, Hakan; Yen, Chih-Feng; Atabekoglu, Cem; Arici, Aydin; Kayisli, Umit Ali
    JNK(c-Jun N-terminal kinase) is one of the main types of mitogen-activated protein kinases. JNK modulates inflammation and apoptosis in response to stress. Our hypothesis is that temporal and spatial changes in JNK activity regulate inflammation in human endometrium and that fluctuation in estrogen and progesterone levels may play a role in JNK activation. Therefore, we aimed to determine total-(t-) and active-(phosphorylated, p-) JNK expression in endometrial tissues in vivo by immunohistochemistry, and in vitro by immunocytochemistry and Western blot analysis. Immunohistochemistry revealed moderate cytoplasmic and nuclear t-JNK immunoreactivity, and mostly nuclear p-JNK immunoreactivity throughout the menstrual cycle and early pregnancy. The highest p- and t-JNK immunoreactivity was detected in late secretory phase (P < 0.05). We observed that endometrial stromal cell (ESC)s showed a significant increase in p-JNK expression following 48 h of estrogen combined with progesterone (E-2 + P-4) withdrawal from the culture conditions, compared to control and non-withdrawal groups (P < 0.05). Upon treatment with JNK inhibitor SP600125, we observed a significantly decreased interleukin (IL)-8 level (P < 0.05) in the presence and absence of E-2. These results demonstrate that JNK expression increases during the late secretory phase when the inflammatory response is highest. Inhibition of IL-8 expression by SP600125 suggests that JNK is involved in regulation of proinflammatory mediators of endometrium.
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    Expression and role of interleukin-23 in human endometrium throughout the menstrual cycle and early pregnancy
    (Elsevier Ireland Ltd, 2010) Uz, Yesim Hulya; Murk, William; Yetkin, Celal Emre; Kayisli, Umit Ali; Arici, Aydin
    Interleukin-23 (IL-23) is a novel cytokine involved in the regulation of organ-specific immune responses. We hypothesized that expression of IL-23 in the human endometrium is menstrual cycle and pregnancy dependent, and is involved in endometrial immune regulation. IL-23 expression and regulation was investigated in the human endometrium and placenta in vivo using immunohistochemistry and in vitro using Western blot and cell viability analyses. IL-23 immunoreactivity in endometrial glandular cells was highest in the late proliferative and early secretory phases, as compared to other cycle phases and first trimester tissues. Endometrial stromal cells (ESC) showed weak IL-23 immunoreactivity without significant changes in intensity and distribution throughout the menstrual cycle. First trimester decidual cells revealed significantly stronger IL-23 staining compared to ESC from non-pregnant endometrium. Both villous cytotrophoblasts and syncytiotrophoblasts also showed positive IL-23 immunoreactivity, with a higher staining in syncytiotrophoblasts. In the trophoblastic cell line HRT8, IL-23 expression increased in a time-dependent manner, but was undetectable in stromal cells under all treatment conditions. ESC treated with recombinant IL-23 showed significantly decreased IL-8 secretion and cell viability. These results suggest a possible regulatory role for IL-23 in the menstrual cycle and in early pregnancy, although the extent and function of this role are yet to be determined. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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    Expression of interleukin-23 in human endometrium throughout the menstrual cycle and early pregnancy
    (Sage Publications Inc, 2008) Uz, Yesim H.; Murk, William; Kayisli, Umit A.; Arici, Aydin
    [Abstract Not Available]
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    Increased c-Jun N-terminal kinase activation in human endometriotic endothelial cells
    (Springer, 2011) Uz, Yesim Hulya; Murk, William; Bozkurt, Idil; Kizilay, Gulnur; Arici, Aydin; Kayisli, Umit Ali
    Endometriosis is a common inflammatory gynecological disease characterized by the presence of endometrial tissue outside of the uterine cavity. The c-Jun N-terminal kinase (JNK) is a subfamily of the mitogen-activated protein kinases (MAPKs) involved in cellular processes ranging from cytokine expression to apoptosis, and is activated in response to inflammation and cellular stress. We hypothesized that inflammatory cytokines in the peritoneal microenvironment increase JNK MAPK activity in endometriotic endothelial cells, and that human endometrial endothelial cells (HEECs) may be involved in inflammatory pathogenesis of endometriosis. Thus, we evaluated the expression of the total- and phosphorylated-(phospho)-JNK in endometrial and endometriotic endothelial cells in vivo, and in HEECs treated with normal fperitoneal fluid (NPF), endometriotic peritoneal fluid (EPF), and the inflammatory cytokines interleukin-1beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in vitro. Phospho-JNK immunoreactivity in HEECs in normal endometrium was significantly higher in the early proliferative and late secretory phases compared to other phases. Both eutopic and ectopic HEECs from the early secretory phase also revealed higher phospho-JNK immunoreactivity, compared to their respective cycle-matched normal HEECs. Moreover, HEECs treated with EPF showed significantly higher phospho-JNK levels compared to that in HEECs treated with NPF. In conclusion, our in vivo and in vitro findings suggest that increased phosphorylation of JNK in HEECs from women with endometriosis is likely due to high level of IL-1 beta and TNF-alpha in peritoneal fluid; this in turn may up-regulate inflammatory cytokine expression and thus play a role in the pathogenesis of endometriosis.
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    Progestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and-3 expression in term decidual cells: Implications for treatment of chorioamnionitis-induced preterm delivery
    (Endocrine Soc, 2008) Oner, Ceyda; Schatz, Frederick; Kizilay, Gulnur; Murk, William; Buchwalder, Lynn F.; Kayisli, Umit A.; Arici, Aydin
    Context: Chorioamnionitis (CAM)-elicited preterm delivery (PTD) is associated with elevated amniotic fluid levels of IL-1 beta and TNF-alpha. We hypothesized that IL-1 beta and TNF-alpha may induce matrix metalloproteinase (MMP)-1 and MMP-3 activity to promote PTD by degrading decidual and fetal membranes and cervical extracellular matrix. Objective: Our objective was to evaluate: 1) MMP-1 and MMP-3 expression in decidual sections from uncomplicated term, idiopathic preterm, and CAM-complicated deliveries, and 2) the separate and interactive effects of IL-1 beta, TNF-alpha, medroxyprogesterone acetate (MPA), and a p38 MAPK inhibitor (SB203580) on MMP-1 and MMP-3 expression in term decidual cells (DCs). Interventions and Main Outcome Measures: Decidua were immunostained for MMP-1 and MMP-3. Cultured term DCs were incubated with estradiol (E2) or E2 plus MPA with or without IL-1 beta or TNF-alpha with or without S13203580. ELISA and Western blotting assessed secreted MMP-1 and MMP-3 levels, quantitative real-time RT-PCR assessed mRNA levels, and substrate gel zymography was used to determined MMP-1 and MMP-3 proteolytic activity. Results: MMP-1 and MMP-3 immunostaining was more prominent in CAM-complicated decidua vs. control preterm and term decidual specimens (P < 0.05). Compared with basal outputs by DCs incubated with E2, TNF-a enhanced MMP-1 and MMP-3 secretion by 14 +/- 3- and 9 +/- 2-fold, respectively, and IL-1 beta increased MMP-1 and MMP-3 secretion by 13 +/- 3- and 19 +/- 2-fold, respectively (P < 0.05). Addition of MPA lowered basal MMP-1 and MMP-3 outputs by 70%, whereas the TNF-alpha- and IL-1 beta-enhanced MMP-1 and MMP-3 levels were blunted by more than 50% (P < 0.05). SB203580 suppressed TNF-alpha- and IL-1 beta-induced MMP-1 and MMP-3 secretion by severalfold. Western blotting confirmed the ELISA results, and mRNA levels corresponded with MMP-1 and MMP-3 protein levels. MMP-1 and MMP-3 proteolytic activity was confirmed by substrate gel zymography. Conclusion: Augmented DC-expressed MMP-1 and MMP-3 in CAM-complicated pregnancies may promote PTD via decidual, fetal membrane, and cervical extracellular matrix degradation. Effects of progestin-p38 MAPK signaling inhibition on cytokine-enhanced MMP-1 and MMP-3 expression in term DCs suggest alternative mechanisms to prevent CAM-induced PTD.