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Considerable evidence supports that the CD4+ T cell-mediated immune response contributes to the development of atherosclerotic plaque. However, the effects of Th17 cells on atherosclerosis are not thoroughly understood. In this study, we evaluated the production and function of Th17 and Th1 cells in atherosclerotic-susceptible ApoE−/− mice. We observed that the proportion of Th17 cells, as well as Th1, increased in atherosclerotic ApoE−/− mice compared with nonatherosclerotic wild-type littermates. In ApoE−/− mice with atherosclerosis, the expression of IL-17 and retinoic acid-related orphan receptor γt was substantially higher in the arterial wall with plaque than in the arterial wall without plaque. Increased Th17 cells were associated with the magnitude of atherosclerotic plaque in ApoE−/− mice. Importantly, treatment of ApoE−/− mice with neutralizing anti–IL-17 Ab dramatically inhibited the development of atherosclerotic plaque, whereas rIL-17 application significantly promoted the formation of atherosclerotic plaque. These data demonstrate that Th17 cells play a critical role in atherosclerotic plaque formation in mice, which may have implications in patients with atherosclerosis.

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Abstract. Programmed cell death 4 (PDCD4) was recently identified as a novel tumor suppressor gene. The loss of PDCD4 expression was found in several types of human cancer cell lines. To date, however, the status of PDCD4 expression in human glioma tissue is not known. In the present study, the expression of PDCD4 in 30 glioma samples was determined at both mRNA and protein levels by means of RT-PCR, Western blotting, and immunohistochemistry. Herein, we demonstrate, for the first time, that 47% (14/30) of glioma samples lost the expression of PDCD4 mRNA, and 77% (23/30) of glioma samples lacked the PDCD4 protein expression, whereas adjacent normal glial tissues expressed high levels of PDCD4 mRNA and protein. Furthermore, the loss of PDCD4 expression does not significantly correlate with the pathological and clinical features of the glioma. Our new data suggest that the loss of PDCD4 expression is a frequent event in human glioma and may partially contribute to the development of the tumor. IntroductionHuman gliomas are the most common tumor that arises in the central nervous system. As nearly half of gliomas are histologically malignant, therapy of gliomas is one of the most formidable challenges in human malignancies. Over the past two decades, the overall survival of patients suffering from the disease has been improved little, despite therapeutic strategies to employ surgery in combination with radiation and chemotherapy (1,2). Therefore, studies of the molecular biology of the tumor are key issues to getting insight into the mechanisms underlying the pathogenesis of glioma and, in turn, leading to effective therapeutics finally. In recent years, there has been considerable progress in understanding the genetic alterations that cause the initiation and progression of gliomas (3). It is now known that malignant gliomas arise from a number of well-characterized genetic alterations and activations of oncogenes and inactivation of tumor suppressor genes (1). Programmed cell death 4, PDCD4, was recently identified as a novel tumor suppressor gene. To date, however, its role in human glioma is not clear.PDCD4 was first cloned as a gene whose elevated expression is associated with the occurrences of apoptosis in mouse cell lines (4). Subsequently, certain other different mammalian homologues of PDCD4 were identified. So, PDCD4 represents a new pre-apoptotic gene. It is generally accepted that cancer is a disease with deregulated cell proliferation, abnormal differentiation and disturbed apoptosis (5). Thus, it is conceivably inferred that PDCD4 may exert a crucial role in the mechanisms underlying carcinogenesis. Indeed, the following studies demonstrated that PDCD4 was able to inhibit tumor promoter-induced transformation in the mouse JB6 model system (6-8), thereby confirming that PDCD4 acts as a novel tumor suppressor gene. Furthermore, previous studies have shown that PDCD4 exerted its antitumor roles via regulating signal transduction pathways (9,10).Human PDCD4 is first cloned from a human glioma library, wh...

BackgroundTumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues.ResultsIn present study, we provide evidence that TIPE2 inhibits effectively human hepatocellular carcinoma metastasis. The forced expression of TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration and invasion in vitro and suppresses growth and metastasis of HCC in vivo. Clinical information from a cohort of 112 patients reveals that loss or reduced expression of TIPE2 in primary HCC tissues is significantly associated with tumor metastasis. Mechanically, TIPE2 inhibits the migration and invasion through targeting Rac1 and then reduces F-actin polymerization and expression of matrix metallopeptidase 9 (MMP9) and urokinase plasminogen activator (uPA).ConclusionOur results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2 will be a new target for HCC therapy.

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Renal macrophages (RMs) participate in tissue homeostasis, inflammation and repair. RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions and metabolic states of these two RM populations remain unclear. Here we investigate and characterize RMs at different ages by conditionally labeling and ablating RMs populations in several transgenic lines. We find that RMs expand and mature in parallel with renal growth after birth, and are mainly derived from fetal liver monocytes before birth, but self-maintain through adulthood with contribution from peripheral monocytes. Moreover, after the RMs niche is emptied, peripheral monocytes rapidly differentiate into BMRMs, with the CX3CR1/CX3CL1 signaling axis being essential for the maintenance and regeneration of both EMRMs and BMRMs. Lastly, we show that EMRMs have a higher capacity for scavenging immune complex, and are more sensitive to immune challenge than BMRMs, with this difference associated with their distinct glycolytic capacities.