TLR4 (Toll-like receptor 4) and B7-H1, which were known to be restricted to immune cells in the past, were found to be aberrantly expressed in a majority of tumor cells, facilitating tumor evasion from immune surveillance. Our study demonstrated that activation of TLR4 signaling in bladder cancer cells up-regulated B7-H1 expression. Furthermore, this regulation was significantly attenuated by ERK or JNK inhibitor. Our results elucidated the molecule mechanism of regulation of B7-H1 expression through TLR4 signaling and may suggest new strategies of down-regulating the cancer-associated B7-H1 expression for bladder cancer treatment.

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The tumorigenicity of embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells is a major obstacle for clinical translation. Although teratoma formation can be reduced by in vitro pre-differentiation of ESCs, proliferating neural progenitors can generate tumors, especially under the immunosuppressive treatment. In our present study, we used undifferentiated embryonic stem cells as a worst-case model for teratoma formation and study if niche microenvironment of stem cell growth is a crucial driving force in teratoma development. We demonstrate herein that syngeneic ESC transplants recruit bone marrow (BM)-derived macrophages that produce macrophage migration inhibitory factor (MIF), thereby stimulating angiogenesis and teratoma development. Moreover, we show that teratoma angiogenesis relies on preexisting host endothelial cells and does not require BM-derived endothelial progenitors or endothelial cells differentiated from ESCs. Furthermore, ESCs differentiate into pericytes and pericyte coverage is restricted in MIF KO Mice. Genetic deletion of MIF from the host but not from ESCs specifically reduces angiogenesis and teratoma growth. BM cell-derived MIF contributes to teratoma development and blockade of MIF effectively reduces teratoma development after ESC transplantation. This is the first study to demonstrate that syngeneic ESC transplantation provokes an inflammatory response that involves the rapid recruitment of BM-derived macrophages. We propose that infiltrating inflammatory macrophages form niche microenvironments that may be a crucial driving force in the initiation and progression of teratomas.

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by systemic metabolic disorders such as hyperglycemia, insulin resistance, and obesity. The relationship between NAFLD and systemic metabolic disorders has been well reviewed before, however, the metabolic changes that occur in hepatocyte itself have not been discussed. In NAFLD, many metabolic pathways have undergone significant changes in hepatocyte, such as enhanced glycolysis, gluconeogenesis, lactate production, tricarboxylic acid (TCA) cycle, and decreased ketone body production, mitochondrial respiration, and adenosine triphosphate (ATP) synthesis, which play a role in compensating or exacerbating disease progression, and there is close and complex interaction existed between these metabolic pathways. Among them, some metabolic pathways can be the potential therapeutic targets for NAFLD. A detailed summary of the metabolic characteristics of hepatocytes in the context of NAFLD helps us better understand the pathogenesis and outcomes of the disease.