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M Kurimoto

Publications and source records attributed to M Kurimoto.

At least 181 records · Page 10Linked to original sources
PubMed1997

Characterization of anti-human interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) monoclonal antibodies and their application in the measurement of human IL-18 by ELISA.

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel cytokine, which is a potent inducer of IFN-gamma production and plays an important role in Th1 responses. In order to develop a specific ELISA for the measurement of human IL-18, we established 13 anti-human IL-18 monoclonal antibodies and characterized them. 7 murine anti-human IL-18 mAbs and 6 rat anti-human IL-18 mAbs were obtained by fusion of splenocytes from mice or rats immunized with human IL-18, with SP2/0 myeloma cells. These antibodies were classified into 4 groups according to competitive binding ELISAs to the human IL-18 molecule. 1 murine mAb and all 6 rat mAbs neutralized IFN-gamma production induced by IL-18. A specific human IL-18 ELISA was developed using two neutralizing mAbs (#125-2H and #159-12B). This ELISA detects human IL-18 with a minimum detection limit of 10 pg/ml, but does not react with heat-denatured human IL-18. The ELISA does not show any cross-reactivity with other cytokines. Using this assay, human IL-18 was measurable in the plasma of leukemia patients. This ELISA would become a powerful tool for investigating the relationship between IL-18 and various diseases or analyzing the control mechanisms of IL-18 production from IL-18 producing cells.

Adult↗
PubMed1997

Production of IL-18 (IFN-gamma-inducing factor) messenger RNA and functional protein by murine keratinocytes.

Recently, the novel cytokine IL-18 (IFN-gamma-inducing factor) has been described as a growth and differentiation factor for Th1 cells. Epidermal keratinocytes (KC) are known to direct T cell education by production of cytokines. Therefore, expression of IL-18 was sought in KC. Epidermal RNA was analyzed following stimulation with contact sensitizers or controls for IL-18 mRNA expression by semiquantitative reverse transcription-PCR. Constitutive expression of IL-18 mRNA was low in untreated epidermal cells (EC), but early up-regulation of IL-18 mRNA signals was detected following application of a contact allergen in vivo. The peak strength of IL-18 signals was observed within 4 to 6 h following stimulation with an allergen. Application of an irritant (benzalconiumchloride) or solvents did not result in increased signal strength. To determine the cellular origin of IL-18 mRNA in EC, depletion experiments were performed. IL-18 signals were not affected by depletion with anti-CD3 (T cells) or anti-MHC class II mAb-coupled beads identifying KC as a major source of IL-18. These results were confirmed by analysis of mRNA derived from the KC cell line PAM 212. Strong IL-18 signals could be detected by reverse transcription-PCR. To delineate whether IL-18 protein was produced by EC/KC, a sandwich ELISA was used to assay for IL-18 production. Supernatants from allergen-stimulated EC and KC showed production of IL-18 protein. To confirm that IL-18 protein was functional, EC or KC supernatants were tested for their ability to induce IFN-gamma production. Significant amounts of IFN-gamma were detected in supernatants of allergen-treated cells. In aggregate, our data indicate that murine KC are a source of both IL-18 mRNA and functional protein.

Animals↗
PubMed1997

Interleukin-18 activates NF-kappaB in murine T helper type 1 cells.

Interleukin-18 (IL-18) activated T helper type 1 (Th1) cells, OVA#4, and induced production of interleukin-2 (IL-2) in costimulation with anti-CD3 antibody. Upon stimulation with IL-18, IkappaB disappeared from cytoplasm and subsequently nuclear factor-kappaB (NF-kappaB) (p65) accumulated in the nucleus. Corresponding with that, DNA binding activity of NF-kappaB (p65 homodimer or p65/p50 heterodimer) was detected in the nucleus. In the transfection experiments, an IL-2 promoter-driven reporter construct showed the similar responsiveness against IL-18 to that of the intrinsic IL-2 gene, and a construct lacking kappaB site failed to respond to IL-18. These results suggest that IL-18 activates NF-kappaB and it is important for enhancement of IL-2 gene expression by Th1 cells stimulated with IL-18.

Animals↗
PubMed1997

Interleukin-18 (interferon-gamma-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-gamma to inhibit osteoclast formation.

We have established by differential display polymerase chain reaction of mRNA that interleukin (IL)-18 is expressed by osteoblastic stromal cells. The stromal cell populations used for comparison differed in their ability to promote osteoclast-like multinucleated cell (OCL) formation. mRNA for IL-18 was found to be expressed in greater abundance in lines that were unable to support OCL formation than in supportive cells. Recombinant IL-18 was found to inhibit OCL formation in cocultures of osteoblasts and hemopoietic cells of spleen or bone marrow origin. IL-18 inhibited OCL formation in the presence of osteoclastogenic agents including 1alpha,25-dihydroxyvitamin D3, prostaglandin E2, parathyroid hormone, IL-1, and IL-11. The inhibitory effect of IL-18 was limited to the early phase of the cocultures, which coincides with proliferation of hemopoietic precursors. IL-18 has been reported to induce interferon-gamma (IFN-gamma) and granulocyte/macrophage colony-stimulating factor (GM-CSF) production in T cells, and both agents also inhibit OCL formation in vitro. Neutralizing antibodies to GM-CSF were able to rescue IL-18 inhibition of OCL formation, whereas neutralizing antibodies to IFN-gamma did not. In cocultures with osteoblasts and spleen cells from IFN-gamma receptor type II-deficient mice, IL-18 was found to inhibit OCL formation, indicating that IL-18 acted independently of IFN-gamma production: IFN-gamma had no effect in these cocultures. Additionally, in cocultures in which spleen cells were derived from receptor-deficient mice and osteoblasts were from wild-type mice and vice versa, we identified that the target cells for IFN-gamma inhibition of OCL formation were the hemopoietic cells. The work provides evidence that IL-18 is expressed by osteoblasts and inhibits OCL formation via GM-CSF production and not via IFN-gamma production.

Animals↗
PubMed1997

IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12.

We have previously reported the cloning of a novel cytokine, IFN-gamma-inducing factor (IGIF), which shared some biologic activities with IL-12. In this study, we analyzed the effects of murine IGIF on the activation of T cells, and compared the effects with those of IL-12. IGIF alone had no effect on the activation of T cell lines or Th1 clones, while IGIF increased the IFN-gamma production by antigen-stimulated T cell lines, but had no effect on IL-4 or IL-10 production. As reported with IL-12, IGIF served as a costimulatory factor for Th1 clones stimulated with Ag on B cell APC, immobilized anti-CD3, Con A, or IL-2 to augment IFN-gamma production and to induce IL-2R alpha-chain expression and proliferation of the Th1 clones, whereas IGIF had little or no effect on the IL-4 production and proliferation of Th2 clones stimulated with anti-CD3 or Ag. However, IGIF synergized with IL-12 to further augment the IFN-gamma production of the Th1 clones. Even in the presence of saturated amounts of IL-12, IGIF still augmented the IFN-gamma production and proliferation and enhanced the IL-2R alpha-chain expression of the Th1 clones. In contrast with IL-12, IGIF induced IL-2 production by Ag- or anti-CD3-stimulated Th1 clones. These two findings indicate that IGIF and IL-12 are utilizing different signal transduction pathways. We also found that IGIF as well as IL-12 was endogenously released through interaction between Th1 cells and spleen cell APC in the presence of specific Ag, and that it regulated IFN-gamma production. These results further suggest that IGIF may act as an immunoregulatory factor in the immune response.

Animals↗
PubMed1997

Cloning and sequencing of trehalose synthase gene from Thermus aquaticus ATCC33923.

The gene encoding trehalose synthase (catalyzing the conversion of maltose into alpha, alpha-trehalose by transglucosylation) was cloned from Thermus aquaticus ATCC33923. Sequence analysis revealed a 2892 bp synthase gene and a 963 residue amino-acid sequence. The 547 N-terminal residues were homologous to the full-length synthase from Pimelobacter sp. R48 (53.8% identity).

Amino Acid Sequence↗
PubMed1997

Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme.

The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive IL-1beta precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-gamma inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export. Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form. Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to Propionibacterium acnes and lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE-/- mice may account for their protection from septic shock.

Animals↗
PubMed1997

In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites.

Interferon-gamma-inducing factor/interleukin-18 is a novel cytokine that reportedly augments natural killer (NK) activity in human and mouse peripheral blood mononuclear cell cultures in vitro and has recently been designated IL-18. In this study, IL-18 exhibited significant antitumor effects in BALB/c mice challenged intraperitoneally (i.p.) with syngeneic Meth A sarcoma when administered i.p. on days 1, 2 and 3 after challenge. Intravenous (i.v.) administration also induced antitumor effects in the tumor-bearing mice; however, subcutaneous (s.c.) administration did not. When mice were twice pretreated with 1 microg IL-18 3 days and 6 h before tumor challenge, all mice survived whereas control mice died within 3 weeks of challenge. Inhibitory effects on Meth A cell growth in vitro were not observed with either IL-18 or interferon gamma. The effects of IL-18 pretreatment were abrogated by abolition of NK activity after mice had been injected with anti-asialo GM1 antibody 48 h before and, 24 h and 72 h after tumor challenge. Mice pretreated with IL-18 and surviving tumor challenge resisted rechallenge with Meth A cells but could not reject Ehrlich ascites carcinoma, and spleen cells from the resistant mice, but not control mice, exhibited cytotoxic activity against Meth A cells in vitro after restimulation with mitomycin C-treated Meth A cells for 5 days. The effector cells in the spleen cell preparations from resistant mice appear to be CD4+ cells because cytolytic activity was significantly inhibited after depletion of this subset by monoclonal antibodies and complement. In conclusion, IL-18 exhibits in vivo immunologically (primarily NK) mediated antitumor effects in mice challenged with syngeneic Meth A sarcoma and induces immunological memory and the generation of cytotoxic CD4+ cells.

Animals↗
PubMed1997

Immunohistochemical and immuno-electron-microscopic detection of interferon-gamma-inducing factor ("interleukin-18") in mouse intestinal epithelial cells.

The novel cytokine interferon-gamma-inducing factor ("interleukin-18") is produced by macrophage-like cells in mice with endotoxin shock and induces the production of interferon-gamma by T cells in vitro. To determine the physiological role for mouse interferon-gamma-inducing factor, we studied its tissue distribution in several organs (intestine, spleen, thymus, kidney, and liver) in healthy mice of different ages, including fetal stages. Activity of the cytokine in the organ extracts of adult mice was measured by enzyme-linked immunosorbent assay, and the cellular distribution of interferon-gamma-inducing factor in organs from fetal and adult mice was determined by immunohistochemistry. Intestinal extracts of adult mice showed the highest concentrations among the organs studied. Other organ extracts of adult mice showed lower concentrations of the cytokine. Immunohistochemical analysis revealed that interferon-gamma-inducing factor was localized in the cytoplasm of intestinal epithelial cells from fetal and adult mice. These results show for the first time that intestinal epithelial cells may be the main producers of interferon-gamma-inducing factor under normal physiological conditions and suggest that its constitutive expression in intestinal epithelial cells may have an important role in the induction of mucosal immunity.

Animals↗
PubMed1997

Epitope specificity of IgE antibodies to a major allergen (Cry j 1) of Japanese cedar pollen in sera of humans and monkeys with pollinosis.

Japanese cedar (Cryptomeria japonica) pollinosis has been reported to occur naturally in Japanese monkeys (Macaca fuscata) as well as humans. Using monoclonal antibodies (mAb) specific to Cry j 1, a major allergen in Japanese cedar pollen, we identified five independent epitopes (EP-1 to EP-5) on the molecule. The epitopes recognized by IgE antibodies in the sera of humans and monkeys with the pollinosis were analysed by an IgE enzyme-linked immunosorbent assay inhibition method with these mAb. In human patients, the mAb to EP-1 strongly blocked the binding of IgE antibodies in all patients' sera to Cry j 1. The reaction patterns of IgE antibodies in monkeys, however, varied among the troops of monkeys. In some troops, the mAb to EP-1 showed a blocking pattern similar to that for human patients. In other troops, mAb to EP-4 and EP-5 blocked binding of IgE. These results indicate that some, but not all, monkeys have antibody responses to the major allergen similar to those of humans.

Allergens↗
PubMed1997

Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells.

We examined the ability of interleukin-12 (IL-12) and IL-18 to induce the production of gamma interferon (IFN-gamma) and nitric oxide (NO) by murine peritoneal exudate cells (PEC) and to stimulate the growth-inhibitory activity of these cells against Cryptococcus neoformans. PEC produced IFN-gamma and NO when stimulated with a combination of IL-12 and IL-18 but little or no IFN-gamma or NO when either cytokine was used alone. PEC anticryptococcal activity was mediated by IFN-gamma and NO production, since it was completely inhibited by a neutralizing anti-IFN-gamma monoclonal antibody (MAb) and N(G)-monomethyl-L-arginine, a competitive inhibitor of NO synthesis, respectively. To identify the IFN-gamma-producing cells among PEC stimulated with IL-12 and IL-18, we depleted NK cells, gammadelta T cells, or CD4+ T cells by treating PEC with specific Abs and complement. NK cell depletion strongly suppressed IFN-gamma production and almost completely inhibited NO production and anticryptococcal activity, while depletion of other cells had no such influence. Alternatively, purified NK cells by two cycles of glass adherence and magnetic separation with anti-CD3, -CD4, -CD8, and -B220 MAbs produced a greater amount of IFN-gamma by stimulation with IL-12 and IL-18 than unseparated non-glass-adherent PEC. Our results demonstrated that IL-12 and IL-18 synergistically induced NO-dependent anticryptococcal activity of PEC by stimulating NK cells to produce IFN-gamma.

Animals↗
PubMed1997

Responses of monkeys with pollinosis to two major allergens of Japanese cedar pollen.

We examined the responses of two Japanese monkeys with pollinosis to two major allergens (Cry j 1 and Cry j 2) of Japanese cedar pollen. The two monkeys (A and B) had specific IgE antibodies to the allergens and showed a strong positive reaction to both of them in the intradermal test. In the histamine release test with peripheral blood mononuclear cells (PBMC), monkey A showed a typical pattern similar to that seen in human patients, while monkey B released a low level of histamine. The proliferative response of PBMC to both allergens in monkey A was weak, but was typical in monkey B. From clinical as well as immunological points of view, these monkeys may be a suitable animal model for Japanese cedar pollinosis in humans.

Allergens↗
PubMed1997

Cerebrospinal fluid tissue factor and thrombin-antithrombin III complex as indicators of tissue injury after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: No marker that reflects and predicts brain injury due to subarachnoid hemorrhage (SAH) and cerebral vasospasm has been reported. We hypothesized that membrane-bound tissue factor (mTF) and thrombin-antithrombin III complex (TAT) in the cerebrospinal fluid (CSF) of patients with SAH become markers indicating brain injury. To evaluate the hypothesis, we correlated levels of mTF and TAT in the CSF of patients with SAH with clinical severity, the degree of SAH, and outcome. METHODS: We assayed CSF mTF, TAT and myelin basic protein (MBP) in patients with SAH at intervals that included days 0 to 4 and days 5 to 9 after ictus. Classification of clinical severity of disease on admission was based on Hunt and Hess grade, degree of SAH on CT on Fisher's grading, and outcome 3 months after SAH on the Glasgow Outcome Scale. RESULTS: In the interval from days 0 to 4, mTF and TAT correlated with Hunt and Hess and Fisher grades, and occurrence of cerebral infarction due to vasospasm. Only mTF correlated significantly in this period with outcome. TAT, mTF, and MBP all correlated significantly with each other. From days 5 to 9, only mTF correlated with cerebral infarction, infarction volume, MBP levels, and outcome. CONCLUSIONS: Both mTF and TAT reflected brain injury from SAH and predicted vasospasm, though mTF was more sensitive and a better predictor of outcome. Unlike mTF, TAT did not correlate with vasospasm during the interval when it most commonly occurs, which raised doubt about thrombin activation as a cause.

Adult↗
PubMed1997

Synthesis of glycosyl-trehaloses by cyclomaltodextrin glucanotransferase through the transglycosylation reaction.

Cyclomaltodextrin glucanotransferase from Bacillus stearothermophilus produced a series of glycosyl-trehaloses through the transglycosylation reaction with cyclomaltohexaose as the glycosyl donor and trehalose as its acceptor. After beta-amylase treatment, five species of glycosyl-trehaloses were isolated by column chromatography. After chemical and enzymatic analyses, it was concluded that these oligosaccharides were alpha-maltosyl alpha-D-glucopyranoside, alpha-maltotriosyl alpha-D-glucopyranoside, alpha-maltosyl alpha-maltoside, alpha-maltotriosyl alpha-maltoside, and alpha-maltotriosyl alpha-maltotrioside. These were not hydrolyzed by salivary amylase, artificial gastric juice, or pancreatic amylase, however they were hydrolyzed by enzymes of the small intestine.

Carbohydrate Sequence↗
PubMed1997

Synthesis by an alpha-glucosidase of glycosyl-trehaloses with an isomaltosyl residue.

Glycosyl-trehaloses with an isomaltosyl residue were synthesized by alpha-glucosidase from Aspergillus niger by using maltotetraose as a glucosyl donor and trehalose as the acceptor. The one trisaccharide and two tetrasaccharides formed were isolated by successive column chromatography. The results of an enzymatic digestion, methylation analysis, and 13C-NMR studies indicated that these oligosaccharides were alpha-isomaltosyl alpha-glucoside, alpha-isomaltotriosyl alpha-glucoside and alpha-isomaltoside. These oligosaccharides were not fermented to an acid by Streptococcus mutans, and they effectively inhibited water-insoluble glucan synthesis from sucrose by glucosyltransferase. In an in vitro utilization test with human intestinal bacteria, these oligosaccharides were predominantly utilized by Bifidobacteria.

Bacteroides↗
PubMed1997

Leptomeningeal melanoma associated with straight sinus thrombosis--case report.

A 36-year-old female was admitted with leptomeningeal melanoma associated with straight sinus thrombosis manifesting as headache and vomiting. Computed tomography and magnetic resonance imaging showed the subarachnoid space was diffusely enhanced. Her consciousness rapidly deteriorated to a coma. Angiography demonstrated straight sinus thrombosis. Thrombolysis by superselective catheterization and infusion of urokinase was successfully performed. She recovered consciousness, but developed paraparesis 2 weeks later. Malignant melanoma with meningeal dissemination was diagnosed by an open biopsy of the lumbar lesion. Angiitis induced by the infiltration of tumor cells and activation of the blood coagulation cascade was probably the causative mechanism of the sinus thrombosis.

Adult↗
PubMed1997

Co-secretion of parathyroid hormone and parathyroid-hormone-related protein via a regulated pathway in human parathyroid adenoma cells.

Parathyroid-hormone-related protein (PTHrP) is widely expressed not only in malignant tumors but also in both epithelial and nonepithelial cells of normal tissues. Secreted PTHrP is suspected to act as a paracrine or autocrine regulator. However, little is known about its secretory pathway. To cast light on this question, we studied the intracytoplasmic distribution of parathyroid hormone (PTH) and PTHrP immunohistochemically and immunoelectron microscopically in 10 surgically resected parathyroid adenomas. Double immunostaining was performed using anti-PTH antibody and a newly established anti-PTHrP antibody to reveal the relationship between their two distributions. Additional examination by cell immunoblot assay was performed to determine whether both PTH and PTHrP are secreted simultaneously. Both PTH and PTHrP were actually secreted from individual parathyroid cells simultaneously on cell immunoblot assay. Immunohistochemically, there were two different types of adenoma cells, i.e., one positive only for PTH and the other positive for both PTH and PTHrP. PTH was distributed linearly or fine granularly along the cytoplasmic membrane, whereas PTHrP was distributed diffusely or coarse granularly in the cytoplasm. The intracytoplasmic distributions of PTH and PTHrP often overlapped. Immunoelectron microscopical examination demonstrated that PTHrP co-localized with PTH in the same secretory granules. The results clearly demonstrated that PTHrP can be co-secreted with PTH via a regulated pathway using secretory granules.

Adenoma↗