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T Agui

Publications and source records attributed to T Agui.

At least 37 records · Page 2Linked to original sources
PubMed1995

Opposite actions of transforming growth factor-beta 1 on the gene expression of atrial natriuretic peptide biological and clearance receptors in a murine thymic stromal cell line.

The regulation of the gene expression of the atrial natriuretic peptide receptor (ANPR) subtypes, ANPR-A, ANPR-B, and ANPR-C, was investigated in a murine thymic stromal cell line, MRL 104.8a. When MRL 104.8a cells were cultured with transforming growth factor (TGF)-beta1, [125I]ANP binding sites increased with increasing dose of TGF-beta1. These binding sites were identified as ANPR-C by a displacement experiment with ANPR-C-specific ligand, C-ANF, and by the affinity cross-linking of the [125I]ANP binding sites with a chemical cross-linker to determine the molecular weight of the ANPR. This augmentation of the ANPR-C expression was elucidated to occur at the transcriptional level by Northern blot experiment, comparison of the relative amounts of mRNA by reverse transcription (RT)-PCR, and in vitro nuclear transcription assay. Conversely, the expression of the ANP biological receptors, ANPR-A and ANPR-B, was shown to be down-regulated by TGF-beta1. These data suggest that TGF-beta1 regulates the gene expression of ANPRs in the thymic stromal cells and that ANP and TGF-beta1 might affect the thymic stromal cell functions.

Animals↗
PubMed1995

Endothelin-induced interleukin-6 production by rat aortic endothelial cells.

Endothelin (ET) produced by endothelial cells has recently been found to be a potent vasoconstricting hormone. In this paper, ET isopeptides, both ET-1 and ET-3, were shown to be potent stimulators of interleukin (IL)-6 production by a rat aortic endothelial cell clone, WAE-1. Semi-quantitative polymerase chain reaction analysis indicated that augmentation of IL-6 production is due to an increase in IL-6 messenger RNA level. Ligand binding assay indicated that most of the [125I]ET-1 binding sites correspond to ET receptor type A (ETAR). However, ET receptor type B (ETBR) was shown to be also present on this cell line by reverse transcription polymerase chain reaction using ETBR-specific primers and by ligand binding assay using [125I]ET-3, although the protein receptor level is much lower than that of ETAR. ET-1, but not ET-3, induced inositol 1,4,5-triphosphate production and an increase in intracellular Ca2+ concentration with similar dose response. These data suggest that ET-1 stimulates IL-6 production through ETAR-phospholipase C activation axis, whereas ET-3 stimulates IL-6 production through different signaling pathway. The results shown in this paper raise the possibility that ET plays a role in inducing inflammation in endothelium.

Animals↗
PubMed1995

Low level of immunoglobulin G2a subclass correlates with a deficiency in T helper cell function in LEC mutant rats.

Long-Evans Cinnamon (LEC) rats bear a congenital deficiency in CD4+8- thymocytes and consequently a deficiency in helper T cell function. This mutation is caused by a single recessive gene referred to as thid (T helper immunodeficiency). It has been reported that rat immunoglobulin(Ig) G2a subclass is a counterpart of the mouse IgG1. Serum IgG2a levels in LEC rats were ten-fold lower than those of normal rats. To identify a cause of low IgG2a levels in LEC rats, we made backcross rats, (F344 x LEC)F1 x LEC, and examined linkage to the thid mutation. The serum IgG2a levels of rats showing thid/thid phenotype were much lower than those of rats showing +/thid phenotype. This indicates that the thid mutation correlates with low level of IgG2a subclass. Furthermore, LEC rat B cells were shown to secret IgG2a normally when these were stimulated with LPS and IL-4, suggesting that a cause of low level of IgG2a was due to defect of T cell function but not due to B cell disfunction in LEC rats. These results confirm the idea that T-helper (Th) function is necessary for the class switch to IgG2a subclass in rats.

Animals↗
PubMed1994

Expression of major histocompatibility complex class II but not of CD8 molecules by lectin-stimulated peripheral CD4+ T cells in LEC mutant rats.

LEC rats show a congenital maturational arrest from CD4+8+ to CD4+8- but not to CD4-8+ cells in the thymus. However, some CD4+ cells exist in peripheral lymph nodes. In normal F344 rats, a part of CD4+ T cells expressed CD8 molecules upon concanavaline A (Con A) stimulation. The percentage of CD4+8+ cells and the level of CD8 expression in F344 rat CD4+ cells were enhanced by the glucocorticoid hormone dexamethasone. In contrast, although LEC rat CD4+ cells induced DNA synthesis normally upon Con A stimulation, expression of CD8 was significantly reduced. Furthermore, addition of dexamethasone did not restore the inhibition of CD8 expression. However, LEC rat CD4+ cells could induce CD8 expression, when stimulated by T cell receptor (TCR) cross-linking with anti-TCR monoclonal antibody, suggesting that the TCR-mediated signal is normally transduced in LEC rat CD4+ cells. On the other hand, LEC rat CD4+ cells showed normal expression of major histocompatibility complex (MHC) class II antigens, when stimulated by either Con A or TCR cross-linking, indicating that signals for the induction of MHC class II expression are normal in LEC rat CD4+ cells. Activation of peripheral CD4+ cells has been reported to induce simultaneous expression of CD8 and MHC class II molecules in rats. However, our results using LEC rat CD4+ cells suggest that Con A-induced signaling pathways for CD8 and MHC class II expression can be separable.

Animals↗
PubMed1994

Stimulation of interleukin-6 production by endothelin in rat bone marrow-derived stromal cells.

Endothelin (ET) produced by endothelial cells has recently been found to be a potent vasoconstricting hormone. In this report, ET is shown to be a potent stimulator of interleukin-6 (IL-6) production by rat bone marrow (BM)-derived stromal cells. It was also shown that ET increased the level of mRNA for IL-6 in these cells. The two types of ET receptor (R), ETAR and ETBR, were shown to be expressed on both BM-derived stromal cells in culture and ex vivo in BM tissue, suggesting that ET works as a physiologic stimulator of IL-6 production in the BM. It was shown that ETAR is coupled to phospholipase C activation, leading to the production of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG) as second messengers in BM-derived stromal cells. This was corroborated by data showing that IL-6 production in these cells was induced by combined stimulation with ionomycin and phorbol myristate acetate, thereby bypassing the effects of IP3 and DAG, respectively. This is the first report on the hormonal regulation of IL-6 production by BM stromal cells, indicating that hematopoiesis is subject to endocrinologic regulation under physiologic conditions. ET has recently been reported to be produced by macrophages in response to bacterial lipopolysaccharide and human immunodeficiency virus-1 glycoprotein 120. These facts, taken together with our findings, raise the possibility that ET shares the same role of IL-1 as a local cytokine, mediating an intercellular signal between macrophages and BM stromal cells in response to bacterial or viral stimulation.

Animals↗
PubMed1994

The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.

We identified the rat homolog to the human Wilson disease (WD) gene as the gene responsible for hepatitis (hts) in the Long Evans Cinnamon (LEC) rat. A genetic study using fifty-three backcross progenies showed that the rat WD gene detected by Southern blotting using the human WD gene as a probe was tightly linked to the hts phenotype of the LEC rat with no recombination. LEC is a transcriptionally deficient mutant because no transcript of the rat WD gene could be found in the LEC rat by Northern blotting. This rat WD gene was mapped to 16q12.23-12.3 by fluorescence in situ hybridization and mouse x rat somatic cell hybrid analysis.

Animals↗
PubMed1994

Intestinal intra-epithelial lymphocytes in LEC mutant rats.

LEC rat is a novel strain showing a maturational arrest from CD4+8+ to CD4+8- cells but not to CD4-8+ cells in the thymus. In this study, we examined if this mutation affects the differentiation of intestinal intra-epithelial lymphocytes (IEL) in LEC rats. In normal rat IEL, all 4 subsets with respect to the CD4/CD8 expression were observed. The CD4-8+ population was dominant and a unique population, CD4+8+, was observed as already shown in previous papers. Both CD4+8- and CD4+8+ cells were CD3+, TCR-alpha/beta +, CD45RC-, and CD5+, whereas CD4-8+ cells consisted of a heterogeneous population, being CD3+, TCR-alpha/beta +/-, CD45RC+/-, and CD5-. In LEC rat IEL, CD4+8- and CD4+8+ cells existed normally and distribution of CD4/CD8 subsets was not different from that of normal rat IEL. Furthermore, the expression pattern of CD3, TCR-alpha/beta, CD45RC and CD5 was not different from that of normal rat IEL in each subset. These results suggest that maturational arrest of CD4+8- thymocytes does not affect IEL maturation, especially maturation of CD4+8- IEL, suggesting that the IEL maturation mechanism for CD4+8- cells is independent of that of thymocytes.

Animals↗
PubMed1994

Inheritance of immunoglobulin subclass regulator-1 (Igsr-1) in LEC mutant rats.

Long-Evans Cinnamon (LEC) mutant rats were reported to exhibit a deficiency in the serum immunoglobulin (Ig) G1. The phenotype determining the basal level of IgG1 was tentatively designated as immunoglobulin subclass regulator-1 (Igsr-1), and normal rats and LEC rats were categorized into Igsr-1A (normal expression of IgG1) and Igsr-1B (low expression of IgG1), respectively. In this report we examined genetic trait of this phenotype in LEC rats. The serum IgG1 levels in F1 hybrids produced by mating LEC rats (Igsr-1B) with normal rats (Igsr-1A) were intermediate level, indicating that Igsr-1 behaves as a co-dominant genetic trait. When backcross rats were examined, serum IgG1 levels varied between those in normal and LEC rats without clear segregation, indicating that Igsr-1 is controlled by multiple genes. Furthermore, the serum IgG1 level in each backcross rat did not correlate to another recessive mutant genotype, thid (T-helper immunodeficiency). These data suggest that the deficiency in serum IgG in LEC rats is independent of the deficiency in helper T cell function, but might be due to the multiple deficiency in as-yet-unidentified mechanisms.

Animals↗
PubMed1994

Morphological changes in rat aortic endothelial cell line stimulated by endothelin.

We have reported that endothelin (ET)-1 activates interleukin (IL)-6 production in rat aortic endothelial cell line (WAE-1 cell). In this experiment, we investigated the morphological changes induced by ET-1 in cultured WAE-1 cells. The cells were treated with ET-1 for 8 h or 24 h, and then compared with untreated cells by light and electron microscopies. The WAE-1 cells treated with ET-1 for 8 h showed remarkable alterations as following: by light microscopic observation, the cells were enlarged and filled with many vesicles in the cytoplasm, and by electron microscopic observation, the cells showed the increases of nuclear membrane infoldings, increased density of chromatin granules just inside the nuclear membrane, and multivesicular bodies in the cytoplasm. These morphological changes were hardly observed in WAE-1 cells-treated with ET-1 for 24 h. It was suggested that ET-1 stimulated DNA synthesis and secretion of cytoplasmic products in WAE-1 cells.

Animals↗
PubMed1993

Inhibition of the copper incorporation into ceruloplasmin leads to the deficiency in serum ceruloplasmin activity in Long-Evans cinnamon mutant rat.

Although ceruloplasmin is known to be a copper-transporting protein, little is known about the biochemical mechanisms of copper incorporation into ceruloplasmin during the biosynthesis. We have examined various levels of ceruloplasmin biosynthesis in the Long-Evans Cinnamon (LEC) rat, which possesses a mutation causing the deficiency in serum ceruloplasmin activity associated with excess hepatic copper accumulation. Southern and Northern blot analyses revealed that the gene and mRNA encoding ceruloplasmin resided normally in LEC rat liver. Western blot analysis showed a normal level of ceruloplasmin in LEC rat serum. Following metabolic labeling of hepatocytes with 64Cu, no radioactive copper was detected in the ceruloplasmin fraction in LEC rat hepatocytes using Sephadex G-75 column chromatography, indicating that copper incorporation into ceruloplasmin is deficient in the LEC rat. Furthermore, LEC rat hepatocytes incubated with 64Cu also showed a reduction in the efficiency of copper transport from cytosolic to noncytosolic fractions and a reduced copper efflux from the hepatocytes, indicating that LEC rat hepatocytes possess an abnormality in copper metabolism. These results suggest that an abnormality of the copper delivery mechanism causes an inhibition of copper incorporation into the ceruloplasmin molecule in the liver, leading to the deficiency in serum ceruloplasmin activity in the LEC rat. In addition, this abnormality also seems to cause an inhibition of biliary copper excretion. The blocking of these two copper exclusion pathways is thought to lead to excess hepatic copper accumulation in the LEC rat. Thus, the LEC rat should be a good model for studying the biochemical process responsible for copper delivery.

Animals↗
PubMed1993

Maturational arrest from CD4+8+ to CD4+8- thymocytes is caused by the bone marrow-derived cells in LEC mutant rats.

LEC rats exhibit a congenital maturational arrest from CD4+8+ to CD4+8- but not to CD4-8+ cells in the thymus. To elucidate a cause of this mutation, bone marrow (BM) chimera rats were made between LEC and normal (WKAH) rats. In (WKAH-->LEC) BM chimera rats, donor-derived T cells matured normally, suggesting that LEC rat thymic stroma has a normal ability in supporting thymocyte differentiation. On the other hand in (LEC-->WKAH) BM chimera rats, LEC rat BM-derived T cells showed the arrest of maturation from CD4+8+ to CD4+8- cells in spite of having normal functions of WKAH rat-derived thymic stroma. In these chimeric rats, even though the maturational arrest from CD4+8+ to CD4+8- cells occurred in the thymus, CD4+ cells were found in peripheral lymph nodes (LNs), suggesting that these CD4+ cells differentiated extrathymically. These results suggest that the maturational arrest from CD4+8+ to CD+8- thymocytes is caused by BM-derived cells but not by thymic stroma.

Animals↗
PubMed1993

Biochemical polymorphisms in Long-Evans Cinnamon (LEC) inbred strain of rat.

Long-Evans Cinnamon (LEC) rat is an inbred strain of mutant rat which has been proposed to be an animal model for human Wilson's disease. In the present study, 28 genetic marker proteins were analyzed by electrophoresis in sublines of LEC inbred strain held separately by four facilities. As expected, the 27 markers were homozygous and identical in all of examined animals. We further found a novel variant of esterase-2 (ES-2) showing an intermediate mobility between profiles of ES-2A and ES-2C types.

Animals↗
PubMed1993

Biochemical polymorphisms in wild rats (Rattus norvegicus) captured in Oita city, Japan.

The investigation of biochemical markers in wild rats (Rattus norvegicus) is thought to be useful in the efficient establishment of inbred strains with a wide range of genetic variability of wild rats. In this study, 21 marker proteins were analyzed by electrophoresis in nine wild rats captured in Oita city. It was found that eleven marker samples in six animals were heterogeneous. We further found that the investigated wild rat population possessed the interesting polymorphisms of esterase-4 (ES-4) with high frequency, which are very rare in laboratory rats.

Alleles↗
PubMed1993

Dissociation of interleukin-2 production from the cell activation in response to the mitogenic lectin in peripheral CD4+ T cells of LEC mutant rats.

A mutant strain of rat, LEC, exhibits a novel maturational arrest of T cells in the thymus, that is, an arrest of the differentiation from CD4+ CD8+ to CD4+ CD8- cells. However, CD4+ T cells were found to arise in lymph nodes (LN) of LEC rats. These CD4+ T cells were T-cell receptor (TcR)/CD3+ and the cross-linking of either TcR alone or both TcR and CD4 molecules induced [3H]thymidine deoxyribose (TdR) incorporation, similar to functional CD4+ T cells. Stimulation with a T-cell mitogen, concanavalin A (Con A), also induced the [3H]TdR incorporation and interleukin-2 receptor (IL-2R) expression in LEC rat CD4+ T cells. Nevertheless, Con A stimulation did not induce IL-2 production by these cells. However, when the stimulation signals were bypassed by ionomycin and phorbol 12-myristate 13-acetate (PMA), IL-2 was normally produced, suggesting that the IL-2 gene and nuclear factors for the IL-2 gene transcription are normal in LEC rats. These results suggest that signals induced by Con A are separated into the one for IL-2 secretion and the other for cell activation including DNA synthesis and IL-2R expression, and that the former signal transduction is blocked in LEC rat CD4+ T cells. Thus, CD4+ T cells in LEC rat LN might provide a good tool for investigating the regulatory mechanisms of IL-2 production.

Animals↗