Association of IL‐4 −590 T&gt;C polymorphism and risk of renal cell carcinoma in a Chinese population

Zhu, Jian; Ju, Xingrong; Fu, Yan; Qin, Chao; Wang, M.; Ding, Qi; Zhang, Z.; Chen, Yin

doi:10.1111/j.1744-313x.2010.00948.x

Cited by 9 publications

(6 citation statements)

References 35 publications

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“…All these data demonstrate that the IL‐4 −590 C/T genotypes were significantly different between the East Asian and Caucasian population, as also recently mentioned by Zhu et al. [42]. The implications of this heterogeneity underline the necessity of including a local control group when clinical studies are carried out.…”

Section: Discussionsupporting

confidence: 73%

Interleukin‐4 Gene Polymorphisms Confer Behçet’s Disease in Turkish Population

et al. 2011

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Several cytokine genes may play crucial roles in host susceptibility to Behçet’s Disease (BD), because the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the IL‐4 and IL‐4Rα gene polymorphisms with the susceptibility to BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD and 76 healthy control subjects. All genotyping (IL‐4 and IL‐4Rα) experiments were performed using PCR sequence‐specific primers. When compared with the healthy controls, the frequency of IL‐4 −1098 TG and −590 CT genotypes was higher in the patients with BD. Analysis of allele frequencies showed that IL‐4 −1098 G and IL‐4 −590 T alleles were more common in the patients with BD when compared with healthy controls. Also, IL‐4 TTC and haplotypes were found to confer BD. Interestingly, we demonstrated that IL‐4Rα gene polymorphism seems to be associated with the Pathergy test positivity in patients with BD. Our data suggest that IL‐4 gene promoter polymorphisms may affect susceptibility to BD and increase risk of developing the disease. However, in order to confirm and assess the association of IL‐4 and IL‐4Rα gene polymorphisms with the BD, large cohort studies are needed.

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Section: Discussionsupporting

confidence: 73%

Interleukin‐4 Gene Polymorphisms Confer Behçet’s Disease in Turkish Population

et al. 2011

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“…Furthermore, IL-4 has a tremendous impact on the anti-tumor immunity by shifting the Th1/Th2 balance [42]. The importance for IL-4 in RCC is demonstrated by the existence of a functional polymorphism in the IL-4 gene (-590 T) leading to an enhanced expression of this cytokine, which is correlated with an increased risk of developing RCC [43] and a decreased survival [44] when compared to RCC patients carrying the other haplotype (-590C). In contrast to earlier reports, IL-4 can reduce tumor growth suggesting that the time point and local distribution of high IL-4 levels have an impact on RCC progression.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of IL-4 and TNFα on the induction of B7-H1 in renal cell carcinoma cells inhibiting allogeneic T cell proliferation

et al. 2014

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BackgroundThe importance of B7-H molecules for the T cell/tumor communication and its impact on renal cell carcinoma (RCC) progression and prognosis has been recently described. Cytokine treatment of RCC has earlier been shown to be beneficial in preclinical settings, but its clinical implementation has not proven to be as effective. This might be partially explained by the yet incomplete picture of cellular alterations in tumor cells upon cytokine treatment investigated in detail in this study.MethodsRCC tumor cell lines were treated with different cytokines alone or in combination. The constitutive and/or cytokine-induced expression of cytokine receptors signaling components and B7-H molecules in RCC cells were analysed by qPCR and flow cytometry. A mcherry reporter gene construct containing B7-H1 promoter was cloned and its activity was determined upon transfection in cytokine-stimulated cells. Cytokine pretreated tumor cells were co-cultured with allogeneic CD8+ T cells from healthy donors and T cell proliferation as well as cytokine secretion was determined.ResultsA heterogeneous, but constitutive B7-H1,-H2,-H3 and H4 expression was found on human RCC cell lines. IL-4 and TNFα treatment led to strong synergistic induction of B7-H1 in RCC cells, whereas B7-H2 was only increased by TNFα. In contrast, B7-H3 and B7-H4 expression were not altered by these cytokines. Treatment of RCC cells with TNFα and IL-4 was accompanied by an activation of signaling molecules like NF-κB, IκB and STAT6. The cytokine-mediated up-regulation of B7-H1 was due to transcriptional control as determined by an increased B7-H1 promoter activity in the presence of IL-4 and TNFα. Despite HLA class I and LFA-1 were also increased, the cytokine-mediated up-regulation of B7-H1 was more pronounced and caused an inhibition of allospecifc CD8+ T cell proliferation.ConclusionThus, IL-4 and TNFα, which could be released by immune cells of the tumor microenvironment, are able to control the B7-H1 expression in RCC thereby altering T cell responses. These data are of importance for understanding the complex interplay of tumor cells with immune cells orchestrated by a number of different soluble and membrane bound mediators and for the implementation of check point antibodies directed against B7-H1.

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“…The T allele increases IL-4 expression and is associated with elevation of total serum levels of IL-4, whereas the C allele is associated with lower gene expression (Rosenwasser et al, 1995). The frequencies of the T "high expression" allele range between 70% and 85% in Asians and 15% and 25% in Europeans (Anovazzi et al, 2010;Chiang et al, 2007;Gyan et al, 2004;Hegab et al, 2004;Heward et al, 2001;Holla et al, 2008;Huang et al, 2008;Kawashima et al, 1998;Kim et al, 2007;Landi et al, 2007;Nunez et al, 2008;Rosenwasser et al, 1995;Tangteerawatana et al, 2007;Tsezou et al, 2008;Vairaktaris et al, 2007;Yannopoulos et al, 2007;Zhu et al, 2010). This allele has been associated with some types of cancer (Huang et al, 2008;Vairaktaris et al, 2007;Varin and Gordon, 2009).…”

Section: Introductionmentioning

confidence: 92%