Young Im Kim

Enhanced IL-18 expression in common skin tumors

Interleukin-18 (IL-18) has been found to have multiple effects upon various cells involved in inflammatory response. Recently we reported that B16 murine melanoma cells are able to produce IL-18, which is involved in the regulation of intracellular reactive oxygen intermediates (ROI) and Fas-ligand expression, indicating that IL-18 plays key role in the tumor activity of melanoma. In this study, we investigated the pattern of IL-18 expression in the human system. IL-18 production was tested by enzyme linked immunosorbent assay (ELISA) assay in various tumor cell lines, including Raji (Burkitts lymphoma), IM-9 (B lymphoblast), Jurkat (acute T cell leukemia), SK-MES-1 (squamous cell carcinoma (SCC) cell line), SK-MEL-2, G-361, DM-4, and DX-3 (melanoma cell lines). ELISA tests showed that IL-18 was highly expressed in malignant skin tumors such as SK-MES-1, SK-MEL-2, G-361, DM-4, and DX-3 cell lines, thus suggesting that IL-18 production may be associated with the malignancy of skin tumors. Here, we report that enhanced IL-18 expression is positively correlated with malignant skin tumors such as SCC and melanoma, suggesting the importance role of IL-18 in malignancy of skin tumors. Taken together, expression of IL-18 by tumor cells in human skin tissue may provide an important clue to understand the pathogenesis of malignant skin tumors.

Role of follicular dendritic cells in the apoptosis of germinal center B cells

Follicular dendritic cells (FDCs) provide the most obvious source of antigens, which are essential for the differentiation of GC B cells. It has been reported that most proliferating B cells in germinal centers undergo apoptosis. Quantitative histology shows macrophages with apoptotic debris throughout the germinal center, the highest frequency of these cells being found in the dense FDC network. Based on these findings, we hypothesized that FDC may be involved in an apoptotic pathway of the germinal center B cells. To prove this hypothesis, we performed double immunohistochemical analysis using anti-FDC mAb and peanut agglutinin (PNA), with their respective TUNEL kits. Collated data showed that a great proportion of the apoptotic cells, most of which were positive for PNA, were in close contact with FDC, which indicated an interaction between FDC and B cells in the apoptotic pathway. Further studies using double immunohistochemical staining and FACS analyses demonstrated the expression of Fas-ligand (FasL) in a subset of the FDC. These results suggest that FDC may play a role in the apoptosis of germinal center B cells via Fas-FasL interaction.

Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway Is Required for Endometrial Decidualization in Mice and Human

Decidualization is a crucial change required for successful embryo implantation and the maintenance of pregnancy. During this process, endometrial stromal cells differentiate into decidual cells in response to the ovarian steroid hormones of early pregnancy. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) are known to regulate cell proliferation and apoptosis in multiple cell types, including uterine endometrial cells. Aberrant activation of ERK1/2 has recently been implicated in the pathological processes of endometriosis and endometrial cancer. However, the function of ERK1/2 signaling during implantation and decidualization is still unknown. To determine the role and regulation of ERK1/2 signaling during implantation and decidualization, we examine ERK1/2 signaling in the mouse uterus during early pregnancy using immunostaining and qPCR. Interestingly, levels of phospho-ERK1/2 were highest within decidual cells located at the implantation sites. Expression levels of ERK1/2 target genes were also significantly higher at implantation sites, when compared to either inter-implantation sites. To determine if ERK1/2 signaling is also important during human endometrial decidualization, we examined levels of phospho-ERK1/2 in cultured human endometrial stromal cells during in vitro decidualization. Following treatment with a well-established decidualization-inducing steroidogenic cocktail, levels of phospho-ERK1/2 were markedly increased. Treatment with the ERK1/2 inhibitor, U0126, significantly decreased the expression of the known decidualization marker genes, IGFBP1 and PRL as well as inhibited the induction of known ERK1/2 target genes; FOS, MSK1, STAT1, and STAT3. Interestingly, the phosphorylation level of CCAAT/ enhancer binding protein β (C/EBPβ), a protein previously shown to be critical for decidualization, was significantly reduced in this model. These results suggest that ERK1/2 signaling is required for successful decidualization in mice as well as human endometrial stromal cells and implicates C/EBPβ as a downstream target of ERK1/2.

Evolution of VX2 carcinoma in rabbit tibia: magnetic resonance imaging with pathologic correlation

OBJECTIVE To evaluate the evolution of a metastatic bone tumor model with MRI-pathology correlation. MATERIALS AND METHODS VX2 carcinoma was implanted into the tibiae of 20 rabbits. The rabbits were divided into four groups of five (Groups I-IV). MRI was repeated at 1-week interval up to the fourth week, including sagittal T1-weighted image (T1WI), T2-weighted image (T2WI), gadolinium-enhanced fat-suppressed T1WI (GdT1WI), and diffusion-weighted image (DWI). Each group was sacrificed after the imaging, then histological examination for the tibiae with an implanted tumor was performed and MRI-pathologic correlation was done. RESULTS On MRI-pathology correlation, the corresponding findings were as follows; low SI on T1WI, T2WI-tumor cells, fibrosis (1 week); central low SI on T1WI, T2WI, GdT1WI -tumor cells with fibrosis and necrosis; peripheral high SI on T2WI, DWI, GdT1WI-edema, fibrosis (2 weeks); heterogeneous SI with central low SI on T2WI, DWI-tumor cell nests with extensive necrosis, fibrosis; high SI on T2WI along periosteum-periosteal reaction; high SI around low SI and in bone marrow on T2WI, DWI, GdT1WI-edema, fibrosis; low SI on T1WI in surrounding bone marrow-tumor extension (3-4 weeks). CONCLUSION The evolution of VX2 carcinoma model was well depicted on MR imaging. Necrosis and extent of tumor were best depicted on enhanced, fat-suppressed T1-weighted images. Heterogeneity of the tumor, peripheral edema, and fibrosis were represented well on T2-weighted images. Diffusion-weighted imaging could have a role in depicting necrosis in the evaluation of bone tumor.

A multihydrocyclone water pretreatment system to reduce suspended solids and the chemical oxygen demand

AbstractWe experimentally demonstrated that a multihydrocyclone water pretreatment system consisting of three serially connected hydrocyclones reduced suspended solids, the chemical oxygen demand (COD), and the biological oxygen demand (BOD) in muddy seawater and sewage samples. The separation efficiency of the hydrocyclones asymptotically decreased in accordance with the number of hydrocyclone treatment steps. The difference in the variation in the separation efficiency of the samples was caused by variations in the particle density and the radius of the mud and sludge particles. The multihydrocyclone pretreatment system purified the muddy seawater and sewage at a uniform purification speed of about 500 ton/d. The results suggest that the multihydrocyclone system provides an effective environmentally friendly method water pretreatment system, without any chemical processes.

cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis.

Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.