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Öğe Effect of Pro-Inflammatory Cytokine IL-1?, on Urotensin II Gene Expression in Human Lung Cancer Cells(Duzce Univ, 2018) Okuyan, Hamza Malik; Terzi, Menderes Yusuf; Guneri, Cansu Onlen; Kucuk, Meral UrhanObjective: Lung cancer is the deadliest cancer type world-wide. Poor prognosis of lung cancer patients and lack of an effective treatment require detailed understanding of lung cancer pathogenesis. It was highlighted in some studies that U-II is likely to be a biomarker or molecular target for the prevention and treatment of some diseases such as lung cancer. But its molecular action mechanism has not been elucidated yet. In the present study, we aimed to investigate the role of U-II in lung cancer. Methods: In our study, A549 cells were induced with different doses of IL-1 beta at different durations (1, 3 ng/ml; 6, 24 hours). mRNA levels of GAPDH, NF-kappa B1, MMP-1, and U-II were analyzed with RT-qPCR. The Delta Delta Ct (Delta Delta Ct) method was used for data analysis. The analyzed data were expressed as the fold-change. Results: Our results indicate that U-II gene is expressed in A549 cells and IL-1 beta can induce gene expressions of U-II, MMP-1 and NF-kappa B1 in A549 cells. Conclusions: U-II is a promising molecular target in treatment and prevention of lung cancer. Therefore, further studies are needed to enlighten molecular mechanism of U-II in lung adenocarcinoma.Öğe Effects of Erdosteine and Vitamin D in Experimental Rat Kidney Ischemia/Reperfusion Model(Wiley, 2017) Dogan, Hatice; Demir, Enver Ahmet; Tutuk, Okan; Ozgur, Tumay; Kucuk, Meral Urhan; Ozcan, Oguzhan; Bayraktar, Suphi[Abstract Not Available]Öğe Investigation of New Benzimidazole Derivative Compounds' Effects on A549 Cell Line(Inst Tecnologia Parana, 2020) Duran, Gulay Gulbol; Kucuk, Meral Urhan; Algul, Oztekin; Terzi, Menderes YusufChronic inflammation is a common indication of several diseases, e.g. asthma, chronic obstructive pulmonary disease (COPD), atherosclerosis, etc. Benzimidazole derivatives are preferable compounds to design new analgesic and anti-inflammatory substances due to their unique biological features. We aimed to investigate the effect of a newly synthesized benzimidazole derivative, ORT-83, on A549 human lung adenocarcinoma cell line. ORT-83 was synthesized, and a non-cytotoxic concentration of ORT-83 on A549 cells was detected with MTT assay. To analyze the anti-inflammatory effect of ORT-83, an inflammatory cell culture model was established by stimulating A549 cell line with IL1-beta (10 ng/ml). After 2 hours of treatment with IL1-beta to induce inflammation, A549 cells were exposed to ORT-83 (0.78 mu g/ml) for 24 hours. Thereafter gene expression analyses were performed with qRT-PCR. We found that ORT-83 significantly suppressed the gene expression levels of the proinflammatory cytokines; IL-6, NFkB, and TNF-alpha. However, the increased levels of IL-10 (2.8 folds) by IL-1 beta induction did not change after ORT-83 and/or dexamethasone (Dex: positive control) treatments. While Dex; a COX-2 inhibitor, reduced the COX-2 expression level in inflammatory cells from 10.03 folds to 0.71 folds, ORT-83 reduced its level to 4.37 folds. iNOS expression levels did not change in any experimental groups. In conclusion, we showed that ORT-83 exerted its anti-inflammatory effects by repressing the gene expression of proinflammatory cytokines in the inflammation-induced A549 cell line. Although ORT-83 had a weaker COX-2 inhibitory effect compared to Dex, it was shown to be still a strong anti-inflammatory compound.Öğe Investigation of relationship between IL-6 gene variants and hypertension in Turkish population(Springer, 2015) Karaman, Esin; Kucuk, Meral Urhan; Bayramoglu, Aysegul; Gocmen, Semire Uzun; Ercan, Suleyman; Guler, Halil Ibrahim; Kucukkaya, YunusHypertension (HT) is a common and life threating health problem worldwide leading to stroke, heart attack and renal failure. It is characterized by elevated blood pressure forced heart load. Human interleukin-6 (IL-6) and C- reactive protein (CRP) are known to be involved in inflammatory processes. IL-6 gene is a polymorphic gene which -174 G/C is a common and -572 G/C is a rare polymorphisms identified in promoter region. Publications on IL-6 gene polymorphisms raised the question whether this gene polymorphisms lead to susceptibility to HT or not. To investigate the effects of IL-6 gene -174 G/C (rs 1800795) and -572 G/C (rs1800796) polymorphisms on plasma IL-6 and CRP levels and their associations with hypertension disease in Turkish population we analyzed -174 G/C and -572 G/C polymorphisms and plasma IL-6 and CRP levels in 111 healthy controls and 108 hypertension patients from Adyaman, Turkey. We determined the genotypes using polymerase chain reaction-restriction fragment length polymorphism and analyzed plasma levels of IL-6 by ELISA and CRP by automated standard biochemical methods. We have found no statistically significant differences between IL-6 gene -174 G/C and -572 G/C genotypes and allelic frequencies and IL-6 and CRP plasma levels and HT (p > 0.05). No CC genotype was found in control subjects for -572 G/C polymorphism. In conclusion, we found relation to -174 G/C and -572 G/C gene variants between neither IL-6 and CRP levels nor hypertension. The -572 G allele and GG genotype are predominant in Turkish population in Adyaman, Turkey whereas the CC genotype is very rare.Öğe Role of ACE I/D gene polymorphisms on the effect of ramipril in inflammatory response and myocardial injury in patients undergoing coronary artery bypass grafts(Springer Heidelberg, 2014) Kucuk, Meral Urhan; Sucu, Nehir; Firat, Seyhan Sahan; Aytacoglu, Barlas Naim; Vezir, Ozden; Bozali, Caner; Canacankatan, NecmiyeAngiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms. The study group (n = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril (n = 51) constituted the controls. TNF alpha, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR. Differences between the groups were significant at t4 for the TNF alpha and at t3 for IL-6 (p < 0.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant (p < 0.05). However, differences between the groups were insignificant (p > 0.05). The IL-6, IL-8, TNF alpha, and TnT serum levels had no correlation with the ACE I/D gene polymorphism. Low cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism.
