The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis.

In conjunction with the classical functions of regulating intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization of vitamin D, the population-based association between low vitamin D status and increased cancer risk is now generally accepted. Inflammation is causally related to oncogenesis. It is widely thought that vitamin D plays an important role in the modulation of the inflammation system by regulating the production of inflammatory cytokines and immune cells, which are crucial for the pathogenesis of many immune-related diseases. Mechanistic studies have shown that vitamin D influences inflammatory processes involved in cancer progression, including cytokines, prostaglandins, MAP kinase phosphatase 5 (MKP5), the nuclear factor kappa B (NF-κB) pathway, and immune cells. Multiple studies have shown that vitamin D has the potential to inhibit tumor development by interfering with the inflammation system. The present review summarizes recent studies of the mechanisms of vitamin D on regulating the inflammation system, which contributes to its potential for cancer prevention and therapy. This review helps answer whether inflammation mediates a causal relationship between vitamin D and tumorigenesis.

Ectopically expressed IBP promotes cell proliferation in oral squamous cell carcinoma.

IFN regulatory factor 4 binding protein (IBP) has been shown to play an important role in the progression of malignant tumors such as breast cancer cells, but its function in oral squamous cell carcinoma (OSCC) remains unclear. We found that IBP ectopically expressed in some OSCC specimens but not in normal oral mucosa epithelium tissues. IBP expression was significantly correlated with tumor size, differentiation, clinical stage, and distant metastasis. Furthermore, IBP markedly promoted OSCC cell proliferation, shortened the G1 interval in the cell cycle, and increased cyclin D1 expression. These findings suggest that IBP may be a potential therapeutic target for OSCC.

Ultrasensitive electrochemical strategy for NT-proBNP detection with gold nanochains and horseradish peroxidase complex amplification.

A novel electrochemical immunosensor for sensitive detection of cardiac biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) is fabricated based on the nanostructural gold and carbon nanotubes composite as desirable platform for the capture antibodies immobilization and gold nanochains (AuNCs) and horseradish peroxidase (HRP) complex labeled secondary antibodies (AuNCs-HRP-Ab(2)) for signal amplification. The gold nanochains were prepared by the employment of L-ascorbic acid (AA) as a mediator and template. With the surface area enhancement by nanostructural gold functionalized carbon nanotubes composite, the amount of immobilized primary antibodies (Ab(1)) can be enhanced. More importantly, enhanced sensitivity can be achieved by introducing the multibioconjugates of AuNCs-HRP-Ab(2) onto the electrode surface through "sandwich" immunoreactions. The linear range extended from 0.02 to 100 ng/mL with a correlation coefficient of R=0.997 and a limit of detection reaching 6 pg/mL at a signal-to-noise ratio of 3:1, which is well below the commonly accepted concentration threshold (0.1 ng/mL) used in clinical diagnosis. The specificity, regeneration and stability test demonstrated the feasibility of the developed immunoassay, which gives the attractive characteristics to be a candidate for the detection of NT-proBNP and other proteins of interest in both fundamental and applied research.

[Preparation and characterization of rabbit anti-human apurinic/apyrimidinic endonuclease(APE1) polyclonal antibody].

AIM: To prepare a rabbit anti-human apurinic/apyrimidinic endonuclease polyclonal antibody and then have its characterization analyzed. METHODS: A rabbit polyclonal antibody was prepared through a modified rapid immune procedure and then it was purified using a specific avidity column. The efficacy of this antibody was detected by ELISA, Western blot and immunohistochemistry. RESULTS: The titer of the antiserum determined by ELISA was up to 1:128,000. The kaff value of the antibody was 8.96 x 10(-6) mol/L. Western blot analysis showed the antibody was of high specificity. The final purified antibody was highly specific to native form of APE1 protein in mice and rats. CONCLUSION: The rabbit anti-human APE1 polyclonal antibody with high titer and specificity has been successfully prepared. It can be used not only to elucidate the roles of APE1 protein in many important cellular procedures, but also to detect the expression of the APE1 protein in mice and rats.

Regulation of lymphocyte apoptosis by interferon regulatory factor 4 (IRF-4).

To ensure that homeostasis of the immune system is maintained, the sensitivity of lymphocytes to Fas-mediated apoptosis is differentially regulated during their activation. The molecular mechanisms that link the activation program of lymphocytes to changes in sensitivity to Fas-mediated apoptosis have, however, not been fully characterized. In these studies, we have investigated whether Fas-mediated apoptosis can be regulated by interferon regulatory factor 4 (IRF-4), a lymphoid-restricted member of the IRF family of transcription factors. IRF-4 expression is upregulated during lymphocyte activation and IRF-4-deficient mice have defects in both lymphocyte activation and homeostasis. Here, we show that stable expression of IRF-4 in a human lymphoid cell line that normally lacks IRF-4 leads to a significantly enhanced apoptotic response on Fas receptor engagement. A systematic examination of the downstream effectors of Fas signaling in IRF-4-transfected cells demonstrates an increased activation of caspase-8, as well as an increase in Fas receptor polarization. We demonstrate that IRF-4-deficient mice display defects in activation-induced cell death, as well as superantigen-induced deletion, and that these defects are accompanied by impairments in Fas receptor polarization. These data suggest that IRF-4, by modulating the efficiency of the Fas-mediated death signal, is a novel participant in the regulation of lymphoid cell apoptosis.

Modulation of T cell cytokine production by interferon regulatory factor-4.

Production of cytokines is one of the major mechanisms employed by CD4(+) T cells to coordinate immune responses. Although the molecular mechanisms controlling T cell cytokine production have been extensively studied, the factors that endow T cells with their ability to produce unique sets of cytokines have not been fully characterized. Interferon regulatory factor (IRF)-4 is a lymphoid-restricted member of the interferon regulatory factor family of transcriptional regulators, whose deficiency leads to a profound impairment in the ability of mature CD4(+) T cells to produce cytokines. In these studies, we have investigated the mechanisms employed by IRF-4 to control cytokine synthesis. We demonstrate that stable expression of IRF-4 in Jurkat T cells not only leads to a strong enhancement in the synthesis of interleukin (IL)-2, but also enables these cells to start producing considerable amounts of IL-4, IL-10, and IL-13. Transient transfection assays indicate that IRF-4 can transactivate luciferase reporter constructs driven by either the human IL-2 or the human IL-4 promoter. A detailed analysis of the effects of IRF-4 on the IL-4 promoter reveals that IRF-4 binds to a site adjacent to a functionally important NFAT binding element and that IRF-4 cooperates with NFATc1. These studies thus support the notion that IRF-4 represents one of the lymphoid-specific components that control the ability of T lymphocytes to produce a distinctive array of cytokines.