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Eri Hashimoto

Publications and source records attributed to Eri Hashimoto.

12 recordsLinked to original sources
PubMed2026

MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.

Immune checkpoint inhibitors show insufficient efficacy against pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment (TME) has a remarkable influence on responsiveness to cancer immunotherapy. The aim of this study was to investigate immunosuppressive characteristics of TME in PDAC tissues. The flow cytometry (FCM) of PDAC surgical specimens revealed that the profile of tumor-infiltrating leukocytes was classified into myeloid cell- and T-cell-dominant subtypes; the myeloid subtype was associated with poorer patient outcomes. Myeloid-derived suppressor cells (MDSCs) showed the highest hazard ratio among various myeloid cell types. Single-cell RNA sequencing and FCM revealed that most MDSCs, but not lymphocytes, in PDAC tissues characteristically express CD74. Macrophage migration inhibitory factor (MIF), a CD74 ligand, was highly expressed in cancer-associated fibroblasts (CAFs) and cancer cells. Spatial transcriptomics demonstrated that the MIF-CD74+ myeloid cell interaction was recognized in CAF-dominant areas in PDAC tissue. CAFs expressing immune suppressor molecules such as MFAP5 and LRRC15 were consistent with MIF+ CAFs. Furthermore, MIF+ CAFs enhanced the migratory activity of MDSCs and promoted MDSC induction and activation. In the murine model, MDSCs were significantly increased in MIF-expressing PDAC tumors, as were CD74+ M-MDSCs per M-MDSC, confirming in vivo interaction between CD74 and MIF. MDSCs play a crucial role in creating an immunosuppressive TME in PDAC; the MIF-CD74 axis drives interactions between MDSCs and CAFs.

Humans↗
PubMed2005

Ca2+ influx-mediated histamine synthesis and IL-6 release in mast cells activated by monomeric IgE.

We previously demonstrated that histamine synthesis is drastically induced upon sensitization with an anti-DNP IgE clone, SPE-7, in IL-3-dependent mouse bone marrow derived mast cells (BMMC). We found that Ca2+ mobilization induced by SPE-7 exhibited a similar profile to the capacitative Ca2+ entry evoked by thapsigargin. Potentials for activation of mast cells were found to vary between different IgE clones, and a monovalent hapten, DNP-lysine, suppressed the activation induced by SPE-7. Ca2+ mobilization induced by SPE-7 was suppressed potently by the specific store-operated Ca2+ channel inhibitor, SK&F 96365, but not at all by Ca2+ channel inhibitors with more broad spectrum, La3+ and Gd3+, whereas the Ca2+ mobilization induced by Ag stimulation was suppressed by these inhibitors. Ca2+ mobilization was also induced by SPE-7 in in vitro differentiated mast cells, although the increases in histamine synthesis and IL-6 release were smaller than those in BMMC. These results suggest that Ca2+ influx operated by a distinct mechanism from that in Ag stimulation is essential for increased histamine synthesis and IL-6 release in mast cells.

Animals↗
PubMed2005

The effect of ethanol on cell fate determination of neural stem cells.

BACKGROUND: Recent studies have described the possible relevance of impaired neural stem cell (NSC) functions to the pathophysiology of psychiatric disorders, including alcoholism. However, relatively little is known about ethanol's effects on the determination of cell fate in NSCs. In this study, we investigated the effect of ethanol on neuronal and glial differentiation of NSCs. METHODS: Under neuron-inductive culture conditions, NSCs were induced to differentiate and exposed to ethanol for 96 hr. Immunocytochemistry with cell-type-specific markers was performed (microtubule-associated protein 2 (MAP2) for neurons, glial fibrillary acidic protein (GFAP) for astrocytes and O4 for oligodendrocytes). The cells positive to MAP2, GFAP or O4 were counted, and the number of MAP2-positive cells was quantified by enzyme-linked immunosorbent assay (ELISA) following immunostaining with anti-MAP2 (MAP2-ELISA). The alteration of MAP2, GFAP or myelin basic protein (MBP, a marker for oligodendrocytes) expression was evaluated by Western blot analysis. RESULTS: Ethanol exposure increased astrocytic and oligodendrocytic differentiation with a statistically significant difference at 100 mM, while 25 to 100 mM ethanol reduced neuronal differentiation without affecting the viability of NSCs. The enhanced expression of glial markers was revealed by Western blot analysis for GFAP or MBP. CONCLUSIONS: Glial cells are known to increase in response to various kinds of insults to the central nervous system. It is possible that the increase of astrocytes and oligodendrocytes after ethanol exposure is a compensatory mechanism to repair the impaired neural network by promoting neurite outgrowth and increasing newly generated neurons.

Animals↗
PubMed2003

Augmentation of ethanol-induced cell damage and activation of nuclear factor-kappa B by annexin IV in cultured cells.

BACKGROUND: We previously reported that the amount of annexin IV expression was increased in culture cells by exposure to ethanol. Here, to investigate the physiologic role of annexin IV, we analyzed ethanol-induced cytotoxicity and nuclear factor (NF)-kappa B activity by using annexin IV-overexpressed cells. METHODS: Annexin IV overexpression was performed by transfection of expression vector, in which annexin IV complementary DNA was ligated, to culture cells (rat glioma C6 cells and human neuroblastoma SH-SY5Y cells). Ethanol-induced cytotoxicity was assayed by measuring the mitochondrial enzyme (dehydrogenase) activity or trypan blue exclusion. NF-kappa B activity was measured by electrophoretic mobility shift assay with a kappa B-oligonucleotide probe. RESULTS: Ethanol-induced cytotoxicity was increased by overexpression of annexin IV in both C6 cells and SH-SY5Y cells. Annexin IV overexpression augmented ethanol-induced NF-kappa B activation. CONCLUSIONS: Ethanol-induced increase in annexin IV expression might amplify ethanol-induced cytotoxicity via NF-kappa B activation.

Animals↗
PubMed2003

[Einfacher Rausch].

Explore the source record for details and available documents.

Alcoholic Intoxication↗
PubMed2002

Ethanol-induced augmentation of annexin IV in cultured cells and the enhancement of cytotoxicity by overexpression of annexin IV by ethanol.

The annexins are a family of highly homologous Ca(2+) and phospholipid binding proteins. The expressive amounts of several annexins have been shown to alter in certain pathological states such as brain ischemia and Alzheimer's disease. It has been demonstrated that ethanol induces cytotoxicity, which results in brain damage. In this study, we examined the relationship between ethanol-induced cytotoxicity and the intrinsic amount of annexins using cell lines (rat glioma C6 cells and human adenocarcinoma A549 cells). A decrease in the mitochondrial enzyme (dehydrogenase) activity, which is widely used to measure cytotoxicity, was observed with a high concentration of ethanol (200 mM or more) after a 24-h exposure in both C6 and A549 cells. Western blot analysis revealed that the amount of annexin IV was augmented in both cells by ethanol, whereas levels of annexins I and V were unchanged. The amount of annexin IV was augmented with increasing concentration of ethanol. The overexpression of annexin IV in C6 cells by transfection with annexin IV-DNA enhanced ethanol-induced cell lesion and was accompanied by NFkappaB activation. Thus, it might be indicated that the amount of annexin IV is selectively augmented and this augmentation facilitates the development of cell lesion by ethanol.

Animals↗
PubMed2002

Ethanol-induced augmentation of annexin IV expression in rat C6 glioma and human A549 adenocarcinoma cells.

BACKGROUND: We previously reported that the amount of annexin IV significantly increased in the postmortem brains of alcoholics compared with controls. To investigate further whether ethanol directly affects cellular expression of annexins in a cell, we used cell lines and compared the amounts of annexins between ethanol-exposed and control cells. METHODS: Two kinds of cells (rat glioma C6 cells and human adenocarcinoma A549 cells) were used in the present study. Western blot analysis was performed to quantify expressed amounts of annexins using anti-annexin I, IV, and V antibodies. The mitochondrial enzyme (dehydrogenase) and caspase 3 activities were measured to assess cell damage (apoptosis) by ethanol. RESULTS: Expressive augmentation of annexin IV was shown in both C6 and A549 cells after a 5-hr exposure to 200 mM of ethanol, whereas amounts of annexins I and V were not changed. Both the mitochondrial dehydrogenase and caspase 3 activities were altered under the same conditions in C6 cells, indicating the induction of cell damage (apoptosis), whereas both of these enzyme activities were unchanged in A549 cells under the same conditions. CONCLUSIONS: The amount of annexin IV seemed to increase before the induction of cell damage by ethanol. Annexin IV might be one of the specific markers for the effect of ethanol.

Adenocarcinoma↗
PubMed2002

[Epidemiological study on tobacco smoking and dependence in Hokkaido Prefecture].

A 1998 national survey of smoking and health problems reported that 18 million Japanese over 15-years-old, 53.9% of regular smokers in Japan, have tobacco dependence. The survey used the Tobacco Dependence Screening Questionnaire (TDS), the items in which do not strictly follow the criteria for ICD-10 dependence syndrome. In this study, to evaluate the validity of screening with the TDS for ICD-10 tobacco dependence, TDS and a questionnaire, consisting of items obtained from the ICD-10 dependence syndrome for tobacco use were administered to 1371 participants. The prevalence of tobacco dependence diagnosed according to the ICD-10 criteria was 20.9%. On the other hand, the ratio of tobacco dependence screened by the TDS was 60.1%. Furthermore, only 26.0% of participants screened as tobacco dependent by the TDS were diagnosed as being tobacco dependence according to ICD-10 criteria. These results indicate the possibility of overestimation of the rate of tobacco dependence using the TDS.

Adult↗