Do Leukaemia Inhibitory Factor and Vascular Endothelial Growth Factor Have Any Roles in Intrauterine Device Mechanism of Action? An Experimental Rat Study

2015 ◽  
Vol 81 (2) ◽  
pp. 181-185
Author(s):  
Bulent Cakmak ◽  
Sinan Sabit Ozalp ◽  
Mustafa Fuat Acikalin ◽  
Mehmet Can Nacar
2021 ◽  
pp. 112067212110640
Author(s):  
Dominika Mravec Bencúrová ◽  
Šárka Mandíková ◽  
Pavlína Daňková

Objective To investigate the physiological profile of pro-inflammatory and anti-inflammatory cytokines in tears produced by epithelial cells under the effect of endogenous and exogenous biological factors. Knowing the physiological cytokine profile in tears with its biological characteristics including sex- and age-specific effects is fundamental when tears are analyzed for diagnostic or prognostic purposes in eye diseases. Methods Tear samples were collected from right eye of 45 healthy volunteers (24 males, 21 females) by 5 μl microcapillary tube. Cytokines interleukin 1β, interleukin 10, interleukin 4, interferon gamma, macrophage migration inhibitory factor, and vascular endothelial growth factor were quantified by multiplex Bio-Plex system. Results The production of macrophage migration inhibitory factor cytokine by epithelial cells on the ocular surface is higher in males compared to females ( p = 0.05); actually, most of female tear samples present with undetectable macrophage migration inhibitory factor levels. Our results show the negative correlations between the age and concentrations of interleukin 4 ( p < 0.01) and interferon gamma ( p < 0.01) in tears, respectively, and positive associations of vascular endothelial growth factor levels with the age above 45 years ( p < 0.05). Conclusions Data in this study indicate that age and sex may affect the physiological levels of cytokines in tears. Consequently, the impacts of biological factors need to be recognized and taken into consideration before the levels of cytokines in patients’ tears are analyzed for medical reasons. Concentrations of interleukin 1β and interleukin 10 cytokines, however, are very low in healthy tears and do not seem to be influenced by studied biological factors; therefore, they meet the requirements for analytes suitable for medical diagnostic and prognostic purposes.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4608-4608
Author(s):  
Krzysztof Giannopoulos ◽  
Marcin Omiotek ◽  
Kamila Kosior ◽  
Radoslaw Mlak ◽  
Malgorzata Kowal ◽  
...  

Abstract Abstract 4608 In chronic lymphocytic leukemia (CLL) thalidomide was found to significantly decrease the percentage of regulatory T cells (Tregs) as well the number of CLL cells in vivo. In combination with fludarabine, thalidomide was effective both in refractory/relapse and naïve CLL patients. In our recent clinical trial, we also observed a reduction of vascular endothelial growth factor (VEGF) levels during therapy that were correlated with the reduction of Tregs (r2=0.47, p<0.05). Furthermore, gene expression profiles associated with thalidomide response in CLL revealed several genes involved in angiogenesis (Giannopoulos et al. Leukemia 2009). To further characterize the thalidomide mechanism of action in CLL we assessed expression of neuropilin 1 (NRP1), which is a membrane-bound coreceptor to the tyrosine kinase receptor for both vascular endothelial growth factor (VEGF) and semaphorin (SEMA3A) family members. NRP1 plays versatile roles in angiogenesis, cell survival, migration, and invasion. Recently, NRP1 was also found expressed on plasmacytoid dendritic cells (PDC) as well as on Tregs, two immune cell subpopulations involved in tolerance mechanisms commonly deregulated in tumorigenesis. Our analysis showed NRP1 expression on CLL cells, Tregs and PDC of 38 CLL patients. Using five parameter flow cytometry we found increased expression of NRP1 in CLL when compared to cells derived from healthy volunteers. NRP1 expression was 22.7% on CD5+CD19+ CLL cells vs. 6.2% on CD19+ B cells from controls, p=0.03. Furthermore, we found expression of NRP1 on Tregs as well as PDC with a median expression of NRP1 on Tregs of 42.6 % (range: 10 – 100%). NRP1 was expressed on almost all PDC with a median expression of 100% (range: 98.2 – 100%). In functional studies, we found that NRP1 expression might be regulated by VEGF expression levels. Magnetically separated CLL cells increased expression of NRP1 after cell culture with VEGF. Here, VEGF levels of 0.1 – 0.5ng/ml, which are also observed in primary CLL patient samples, effectively induced expression of NRP1. In accordance, we also observed that VEGF upregulates NRP1 expression on magnetically separated Tregs. However, higher VEGF concentrations inhibited NRP1 expression in CLL cells probably due to a negative feedback loop. In conclusion, we found expression of NRP1 on CLL cells, Tregs as well as PDC in patients with CLL, and we could demonstrate that the expression of NRP1 is regulated by VEGF expression levels. Thus, our previously observed thalidomide-induced reduction of VEGF levels along with a reduced percentage of Tregs in CLL might in part be explained by down-regulation of the NRP1 expression. Disclosures: Stilgenbauer: Hoffmann La Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Travel Grants.


Author(s):  
Ronak Zarei ◽  
Roshanak Aboutorabi ◽  
Bahman Rashidi ◽  
Nahid Eskandari ◽  
Parvaneh Nikpour

Background: Implantation requires intimate crosstalk between the embryo and uterus for a successful establishment of pregnancy. Type 2 diabetes mellitus may lead to implantation failure. The effect of diabetes and its therapeutic drugs on implantation is still largely unclear. Objective: To assess the endometrial expression changes of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF), at the time of implantation in diabetic rats following treatment with Metformin and Pioglitazone. Materials and Methods: Twenty-eight 6-8-wk-old Wistar female rats weighing 200- 250 gr were divided into four groups (n = 7/each). Type 2 diabetes was induced and Metformin and Pioglitazone were applied for 4 wk. The expression of VEGFA and LIF was measured by real-time reverse transcription-polymerase chain reaction and Western blot. Results: The relative expression of VEGFA transcript was higher in the diabetic (p = 0.02) and Metformin-treated (p = 0.04) rats compared to the control group. Furthermore, the VEGFA transcript level significantly reduced in Pioglitazone-treated diabetic rats (p = 0.03). LIF expression was elevated in the Metformin- and the Pioglitazone-treated rats and reduced in the diabetic group in comparison with the control group. Compared to the diabetic rats, the expression of LIF was significantly elevated in the Metformin- (p = 0.01) and Pioglitazone-treated (p = 0.03) groups. Conclusion: The expressions of LIF and VEGFA were altered in diabetic rats during implantation which may be associated with diabetic-related infertility. Pioglitazone is able to restore the VEGFA and LIF expressions to their baseline levels more efficiently than Metformin. Key words: Embryo implantation, Leukemia inhibitory factor, Vascular endothelial growth factor A, Metformin, Pioglitazone, Rats.


2012 ◽  
Vol 172 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Ning Huang ◽  
Homa Ashrafpour ◽  
Ronald H. Levine ◽  
Christopher R. Forrest ◽  
Peter C. Neligan ◽  
...  

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