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T Torigoe

Publications and source records attributed to T Torigoe.

At least 37 records · Page 2Linked to original sources
PubMed1998

Interleukin-10 reduces natural killer sensitivity and downregulates MHC class I expression on H-ras-transformed cells.

We examined the effect of IL-10 on sensitivity to NK-cell-mediated cytotoxicity of the H-ras-induced transformants, W14 and W31. Incubation of cells with recombinant human (rh) IL-10 resulted in a dose-dependent decrease in the expression of MHC class I antigens, but not in the ICAM-1 expression. However, prior incubation of W31 cells with rhIL-10 markedly decreased their susceptibility to cytolysis by rat splenic NK cells. This fact suggested that the IL-10-mediated decrease in MHC class I expression might not dominate the regulation of the NK sensitivity. This was true when rat IL-10 cDNA-introduced W31 cells were used as an endogenous IL-10 producer. The NK sensitivity in vitro of W31T-H, a high IL-10-producer clone, was suppressed downward to the equivalent level of W31 cells pretreated with exogenous rhIL-10. The decreased NK-sensitivity of W31T-H cells was further confirmed by in vivo Winn assay, in which nude mice challenged with W31T-H cells and rat NK cells together developed tumors, whereas nude mice challenged with W31T-L, a minimal-IL-10 producer clone, and NK cells did not. Since neither exogenous nor endogenous IL-10 affected the proliferation of W31 cells, the data indicated that W31T-H cells could evade the NK-cell-mediated immune response in vivo. Taken together, our data reveal a novel mechanism for an IL-10-mediated escape of tumor cells from host immune system by NK cells.

Animals↗
PubMed1998

Intrapulmonary cystic lymphangioma: report of a case.

We describe herein the case of a 52-year-old man found to have a solitary pulmonary lymphangioma. Computed tomography (CT) scan demonstrated a nodule with homogeneous density and a well-defined border in the lower lobe of the right lung. T2-Weighted magnetic resonance imaging (MRI) revealed a nodule with homogeneously high signal intensity. The tumor was removed by partial resection, and pathologic examination confirmed a diagnosis of primary lymphangioma of the lung.

Humans↗
PubMed1998

Localization of pNT22 70 kDa heat shock cognate-like protein in the plasma membrane.

It has been argued that 70 kDa heat shock cognate (hsc73)-like molecules may be expressed on the surface of certain cells, but direct evidence of this has yet to be found. To clarify whether this molecule belongs to hsc73 itself, the membrane protein fraction of Daudi cells was isolated by Triton X-114 phase separation and the reactivity of this membrane protein fraction was assessed with monoclonal antibodies (mAbs) which react with 70 kDa heat shock protein (hsp) family, i.e., NT22, A15 and 3A3. In western blotting analysis, mAb NT22-defined protein (pNT22) was clearly detected as a membrane protein of Daudi cells with an approximate molecular size of 70 kDa, whereas pNT22 was not recognized by anti-cytoplasmic hsc73/hsp72 mAbs A15 or 3A3. By using deleted recombinant hsc73 proteins, it was determined that mAb NT22 recognizes the N-terminal 350-372 amino acid stretches of the hsc73 protein. mAb NT22 also reacted with the cell surface protein of Daudi cells in FACS analysis. Taken together, our present data strongly suggest that pNT22 may be a novel hsc73-like protein that is localized in the plasma membrane.

Antibodies, Monoclonal↗
PubMed1998

BAG-1 and Bcl-2 in IL-2 signaling.

Some cytokines can prolong cell survival in hematolymphoid cells and thus may be crucial for regulation of hematolymphoid cell numbers. It has been shown that mitogenic cytokines can induce not only cellular proliferation but also cellular survival by inhibiting apoptosis in hematolymphoid cells. The signals transduced by these cytokines eventually go to the nucleus and induce expression of their specific target genes. In this context, the induction of anti-apoptotic molecules such as Bcl-2 oncoprotein and BAG-1 protein seems to be a key event for the anti-apoptotic function of cytokines. In T lymphocytes, the interaction of interleukin-2 (IL-2) with its receptor (IL-2R) induces both cellular proliferation and cellular survival. The IL-2R consists of three subunits, i.e., IL-2Ralpha, IL-2R(beta)c, and IL-2R(gamma)c chains. Structure-function analysis of the IL-2R(beta)c chain has revealed that there are at least two functional domains within the subunit. The serine-rich (S) region but not the acidic (A) region within the (beta)c chain is responsible for the mitogenic signaling of IL-2R. The S region is also crucial for the cellular survival signaling, which include the induction of anti-apoptotic gene expressions bcl-2 and bag-l. However, the cellular survival signaling is segregated from the mitogenic signaling in independence from the Jak-family protein kinase activation and rapamycin sensitivity. Segregation of the two signaling pathways of a cytokine receptor has also been shown in receptors of the other mitogenic cytokines. Current topics regarding signal transductions of cytokine receptors responsible for the suppression of apoptosis are discussed in this review.

Animals↗
PubMed1997

Interleukin-2 induces tyrosine phosphorylation of SHP-2 through IL-2 receptor beta chain.

Coupling of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) induces rapid increase in tyrosine phosphorylation of cellular substrates through activation of non-receptor protein tyrosine kinases. Here, we report that stimulation through the IL-2R induced tyrosine phosphorylation of the SH2-containing protein-tyrosine phosphatase SHP-2 in F7, a hematopoietic BAF-B03 transfectant clone expressing the IL-2Rbeta chain. The tyrosine phosphorylation of SHP-2 was specific since another protein-tyrosine phosphatase SHP-1, which is structurally homologous to SHP-2, was not tyrosine phosphorylated. The IL-2-induced tyrosine phosphorylation of SHP-2 required the acidic region within the IL-2Rbeta chain where Src-family PTKs interact. Though the serine-rich region within IL-2Rbeta chain was also required for the phosphorylation of SHP-2, Jak3 activation was dispensable. In COS-7 cells, co-expression of SHP-2 with Lyn resulted in increased tyrosine phosphorylation levels of SHP-2, whereas co-expression of SHP-2 with Fyn failed to alter the levels significantly. Considering that Lyn and Fyn are major Src-family PTKs expressed in BAF-B03 cells, our data suggest that Lyn may be principally responsible for the tyrosine phosphorylation of SHP-2 in F7 cells. Furthermore, the IL-2 stimulation also induced tyrosine phosphorylation of SHP-2 in the human IL-2-dependent T-cell line ILT-Mat. Taken together, these studies demonstrate an involvement of SHP-2 in the IL-2-mediated signaling events through the activation of specific PTKs.

Animals↗
PubMed1996

Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.

BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock cognate protein-like molecule and CD3+, CD4-, CD8-, TCR-alpha beta- killer T cells.

We previously reported that the 70-kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3+, CD4-, CD8-, NKR-P1-, and TCR-alphabeta- T (DNT) killer cells in an MHC class I-unrestricted fashion. We investigated the mechanism of interaction between hsc70 and DNT cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on the cell surface in almost the same density when the cells were growing in a conventional 5% FCS (5% W31) as when the cell growth was inhibited in the cultivation with 1% FCS (1% W31). However, DNT cells lysed only 5% W31, but not 1% W31. Since these observations suggest that certain peptide Ags of the fast growing W31 cells may play a role in the interaction between hsc70 and DNT cells, we pulsed 1% W31 cells with trifluoroacetic acid (TFA)-extracted fast growing W31 tumor Ags of less than 3000 Da in molecular size. We also pulsed 1% W31 with TFA-extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data indicated that DNT cells were clearly cytotoxic to 1% W31 pulsed only with TFA-extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this cytotoxicity. In addition, pronase K treatment of Ags clearly inhibited the cytotoxicity by DNT cells. Taken together, these data suggest that the complex of peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT cells.

Animals↗
PubMed1996

Gastric duplication cyst: evaluation by endoscopic ultrasonography and magnetic resonance imaging.

Endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) are becoming popular methods for examining tumorous lesions along the upper gastrointestinal tract. Though duplication cysts are uncommon, EUS findings from gastric duplication cysts have accumulated and proven very useful for preoperative diagnosis. There have been few reports, however, concerning MRI findings from these cysts. We report herein the case of a 25-year-old man with a gastric duplication cyst. EUS demonstrated a cystic mass adjacent to the fourth layer of the stomach wall. MRI revealed a cyst containing low signal-intensity fluid and high signal-intensity fluid separated by levels. In addition to the characteristic findings from preoperative examinations, the unique histological findings from the cyst are also described.

Adult↗
PubMed1996

Inhibition of natural killer cell cytotoxicity by cell growth-related molecules.

Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H-ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H-ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-gamma clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-1 antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')2 fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.

Animals↗
PubMed1996

Interaction between cell-surface-expressed 70-kilodalton heat shock protein-like antigen and CD3(+)4(-)8(-) killer T cells.

The 70-kilodalton heat shock proteins may be expressed on the cell surface by an unknown mechanism and may interact with CD3+4-8- T cell receptor-alpha beta-killer (DNT) cells. In this interaction, certain cellular nascent or mutant peptides may be important (the complexes of 70-kilodalton heat shock protein and cellular peptides directly interact with DNT cells). The results imply that the interaction between 70 kilodalton heat shock proteins and DNT cells may also work in graft rejection. By using antibodies that react with the cell surface-expressed 70-kilodalton heat shock proteins, one may overcome graft rejection.

Animals↗
PubMed1996

Non-major histocompatibility complex antigen class I-regulatory molecule for cytotoxicity by natural killer cells.

The mechanism of the cytotoxicity by natural killer (NK) cells is not known. It is speculated that there exist several positively regulated and negatively regulated target molecules expressed on the target cell surface. Although one of the latter is considered to be major histocompatibility complex antigen (MHC) class I, in this study we described a novel non-MHC class I molecule that may negatively regulate the NK cytotoxicity. This antigen is defined by monoclonal antibody Cho-1 and is composed of noncovalently associated antigens that are 40 and 200 kilodaltons in molecular size. The expression of this antigen is reduced along with the cell growth induced by growth factors and/or oncogenes. Thus, Cho-1-defined antigen appears to be involved as one of the resistant molecules in the cytotoxic mechanism of NK cells.

Animals↗
PubMed1996

Interleukin-10 inhibited the expression of tumor antigens and major histocompatibility complex antigen on EJ-ras oncogene transformants.

Interleukin-10 (IL-10), a novel inhibitory cytokine, is one of Th-2 (T helper) cytokine. It inhibits mixed lymphocyte reaction, and the production of inflammatory cytokine and monokine downregulates major histocompatibility complex antigen (MHC) class II antigen expression. However, the effect of IL-10 on tumor cells is not known. Therefore, the mechanism of tumor tolerance induced by IL-10 was investigated. (WKA rat fetus-derived fibroblast) (WFB) and W14 and W31 (EJ-ras oncogene transformants of WFB) were cultured with recombinant human (rh)IL-10 (0, 10, 50, 100 ng/ml). FACS analysis was performed using the following monoclonal antibodies: anti-rat MHC class I monoclonal antibody; and monoclonal antibody 109 (anti-natural killer [NK] target molecule on W14). Monoclonal antibody (mAb) 109-defined antigens were newly expressed during the transforming process by EJ-ras oncogene transfection to WFB. In addition, the effects of rhIL-10 on the ability of proliferation and susceptibility to NK cells were assessed. The cultivation with rhIL-10 resulted in a dose-dependent decrease in the expressions of MHC class I antigen and monoclonal antibody 109-defined antigen. The proliferation and susceptibility to NK cells of W14 were inhibited. These data demonstrated a possibility that IL-10 could induce tumor tolerance to host immunity by inhibiting the expression of tumor-associated antigens and MHC class I.

Animals↗
PubMed1996

Immunohistochemical observations of antigen presenting cells and follicular dendritic cells in the tonsil.

In the present study, in order to investigate the behavior in the lymphatic system of phagocytic cells which incorporate potential antigen in the tonsile crypt, the distribution of HRP stained macrophages in the tonsillar system was observed with regard to changes with time. Furthermore, in the tonsillar tissue, in order to investigate the relationship among HRP marked macrophages, follicular dendritic cells and adhesion molecules, such as ICAM-1, immunological double staining was performed. It is open to discussion whether ICAM-1 plays an important role as an adhesive molecule in this migration of macrophages. Immunohistochemical double staining method detected a relation between anti-ICAM-1 antibody positive cells and antigen stained macrophages. In the stained area between anti-ICAM-1 antibodies and anti-DRC-1 antibodies, positive cells were clearly observed to have reticular form, particularly in the mature germinal center. This phenomenon implies that dendritic cells express ICAM-1 on the cell surface to contact other immunorelated cells and/or substances. In the inter-follicular space, anti-ICAM-1 antibody positive cells were observed to form a cluster composed of ICAM-1 positive cells, lymphocytes and HRP stained macrophages. This cluster may be considered the most primary stage of follicles or as triggering the creation of an inmature follicle.

Adult↗
PubMed1996

Two cases with glossopharyngeal neuralgia treated by nerve reaction: oropharyngeal approach.

Two patients with idiopathic glossopharyngeal neuralgia received glossopharyngeal nerve resection by the oropharyngeal method, and their symptoms were relieved. Both patients had suffered proxysms of severe pain in the unilateral glossopharyngeal innervation for many years, and pharmaceutical treatment had been made in vain and, although surgical intervention in one patient had resulted in temporary relief, it had not been possible to prevent recurrence. As the identification of trigger zones by the method of local nerve block caused us to think that surgical treatment would be more effective in both patients, the glossopharyngeal nerve was resected, using the oropharyngeal method, with a view to attaining permanent symptomatic relief. Consequently, satisfactory results were obtained.

Female↗
PubMed1995

70-kDa heat shock cognate protein interacts directly with the N-terminal region of the retinoblastoma gene product pRb. Identification of a novel region of pRb-mediating protein interaction.

Retinoblastoma protein (pRb) functions as a tumor suppressor, and certain proteins are known to bind to pRb in the C-terminal region. Although the N-terminal region of pRb may also mediate interaction with some proteins, no such protein has been identified yet. We demonstrated previously the in vivo protein association between pRb and 73-kDa heat shock cognate protein (hsc73) in certain human tumor cell lines. In this report we analyzed the interaction between these two proteins in vitro. Our data showed that hsc73 interacts with the novel N-terminal region of pRb; that is, pRb binds directly to hsc73 and dissociates from hsc73 in an ATP-dependent manner. By using deletion mutants of cDNA encoding pRb, the hsc73 binding site of pRb was determined to be located in the region (residues 301-372) outside the so-called A pocket (residues 373-579) of this tumor suppressor protein. This finding was compatible with the fact that the adenovirus E1A oncoprotein, which is known to bind to the E2F binding pocket region of pRb, could not compete with hsc73 for the binding. Furthermore, phosphorylation of pRb by cyclin-dependent kinase inhibited the binding of pRb to hsc73. These data suggest that hsc73 may act exclusively as the molecular chaperone for nonphosphorylated pRb. As a result, hsc73 may function as a molecular stabilizer of nonphosphorylated pRb.

Adenosine Triphosphate↗
PubMed1995

IL-2-induced gene expression of protein-tyrosine phosphatase LC-PTP requires acidic and serine-rich regions within IL-2 receptor beta chain.

A protein-tyrosine phosphatase LC-PTP is preferentially expressed in hematopoietic cells and is an early response gene in lymphokine stimulated cells. Here, we found the LC-PTP mRNA induction by IL-2 was markedly inhibited by several tyrosine kinase inhibitors. The induction required both the acidic and serine-rich regions of the IL-2 receptor beta chain (IL-2R beta) in mouse IL-3-dependent pro-B BAF-B03 transfectants. This is strikingly different from the induction of c-myc gene expression, which requires the serine-rich region alone. In addition, overexpression of activated-Lck or -Raf kinases resulted in augmented LC-PTP mRNA expression in myeloid cell line 32D transfectants. Considering the previous findings that the acidic region of the IL-2R beta is responsible for association with Lck and activation of Raf kinase, IL-2-induced expression of LC-PTP mRNA may be primarily transduced through a Lck-Raf mediated signaling pathway.

Animals↗
PubMed1994

Bcl-2 inhibits T-cell-mediated cytolysis of a leukemia cell line.

The bcl-2 gene becomes dysregulated in its expression in a wide variety of human cancers and has been shown to block both spontaneous and drug-induced cell death, thus conferring a selective survival advantage on malignant cells. The biochemical mechanism by which bcl-2 promotes cell survival remains enigmatic but appears to involve a downstream event in an evolutionarily conserved cell death pathway. Here we report that gene transfer-mediated increases in Bcl-2 protein levels in the human leukemia line Jurkat render these cells more resistant to induction of DNA fragmentation and cytolysis by a cloned T-cell. The killing mechanism used by these particular T-cells was consistent with apoptosis, as opposed to necrosis, in that DNA degradation occurred as a prelysis event. The findings raise the possibility that dysregulation of bcl-2 gene expression could play a role in the avoidance of immune surveillance mechanisms by cancer cells.

Animals↗