Biomedical subjects

M Kurimoto

Publications and source records attributed to M Kurimoto.

At least 127 records · Page 7Linked to original sources

PubMed1999

Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees.

To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked antiinflammatory cytokine response (IL-10, soluble tumor necrosis factor [TNF] receptors, IL-1 receptor antagonist) and secretion of alpha-chemokines (IL-8, IFN-gamma-inducible protein 10) and beta-chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-alpha1-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes). IL-12-induced activation of multiple host mediator systems was found only after 8-24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1beta. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.

Animals↗

PubMed1999

Elevated plasma concentrations of interferon (IFN)-gamma and the IFN-gamma-inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis.

Interferon (IFN)-gamma plays an important role in the pathogenesis of sepsis. Production of IFN-gamma is stimulated by synergistic effects of interleukin (IL)-18, IL-12, and IL-15. To investigate the regulation of IFN-gamma production during severe gram-negative infection, the plasma concentrations of IFN-gamma, IL-18, IL-12, and IL-15 were measured in 83 patients with suspected melioidosis. The diagnosis was confirmed in 62 patients, 31 of whom had blood cultures positive for Burkholderia pseudomallei, of whom 12 died. Compared with healthy controls, patients had elevated levels of IFN-gamma, IL-18, IL-12p40, and IL-15 on admission, with significantly higher levels in blood culture-positive patients, and these levels remained elevated during the 72-h study period. In whole blood stimulated with heat-killed B. pseudomallei, anti-IL-12 had a stronger inhibitory effect than anti-IL-18 and anti-IL-15 on IFN-gamma production. This effect of anti-IL-12 was further enhanced by anti-IL-18. These data suggest that during gram-negative sepsis, IFN-gamma production is controlled at least in part by endogenous IL-18, IL-12, and IL-15.

Adolescent↗

PubMed1999

Involvement of interleukin-18 (IL-18) in mixed lymphocyte reactions (MLR).

The in vitro mixed lymphocyte reaction (MLR) is a useful model to study alloresponsiveness to histocompatibility antigens. Secretion of different cytokine proteins in the supernatant of allo-MLR cultures has been reported in a few studies. We studied the levels of the cytokines interferon gamma (IFN-gamma) and interleukin-6 (IL-6), IL-10, IL-12, and IL-18 in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-y, IL-6, IL-10, and IL-18 were detected at 12 h after MLR and markedly increased thereafter. In contrast, secretion of IL-12 was detected after 48-72 h. These results suggested that IFN-gamma production depended on IL-18 in the early phase of MLR and depended on both IL-18 and IL-12 in the late phase. An antibody (Ab) neutralizing test was also performed. The levels of IFN-gamma were significantly downregulated after the addition of anti-IL-18 Ab, anti-IL-12 Ab, or anti-IFN-y Ab, and the levels of IL-12 were significantly downregulated after the addition of anti-IL-12 Ab and anti-IL-18 Ab. Treatment with these Ab did not suppress IL-6 production at all. The two-way MLR showed the same tendency as the one-way MLR. These results suggest the importance of IL-18 and IL-12 in allogeneic cell interactions and also suggest the usefullness of these Ab as regulators of alloresponsiveness.

Culture Media↗

PubMed1999

Oral use of interferon-alpha delays the onset of insulin-dependent diabetes mellitus in nonobese diabetes mice.

Insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetes (NOD) mouse model is thought to be an autoimmune CD4 Th1-like cell-mediated disease. We tested the efficacy of oral use of interferon-alpha (IFN-alpha) therapy on IDDM in NOD mice. Using urine and blood sugar levels as indicators of IDDM, oral administration of murine IFN-alpha (100 IU/body) to NOD mice significantly delayed the onset of symptomatic diabetes. However, oral use of IFN-alpha did not prevent diabetic NOD mice from losing weight once NOD mice were symptomatic, suggesting that orally administered IFN-alpha is a prophylactic rather than therapeutic approach to the management of IDDM.

Adjuvants, Immunologic↗

PubMed1999

Effects of oral administration of interferon-alpha on antibody production in mice with induced tolerance.

In vivo systemic effects and the immunomodulating potential of the oral administration of murine interferon-alpha (IFN-alpha) were investigated through mRNA expression of both IFN-alpha-inducible factors, interferon regulatory factor-1 (IRF-1) and 2,5-adenylate synthetase [2-5(A) synthetase] and 2-5(A) synthetase enzymatic activity in spleen and antibody production. The daily administration of IFN-alpha (0.1, 1, 10, and 100 IU/body) for 1 week augmented IRF-1 and 2-5(A) synthetase mRNA expression levels, as well as 2-5(A) synthetase enzymatic activity in spleen cells but not in cervical lymph nodes. The in vivo immunomodulating potential of the oral administration of IFN-alpha was also evaluated through antibody production in mice with induced tolerance. Ovalbumin (OVA) was administered intraperitoneally (i.p.) to induce systemic antibody production on day 0 when OVA feeding was initiated. The OVA was fed every 2-3 days for a total of 14 doses to suppress serum antibody levels. Oral administration of murine IFN-alpha was initiated on day 0 and was continued for 5 consecutive days weekly for 5 weeks (24 doses). On every sampling date (days 10, 17, 24, and 32), specific antibody levels in the IFN-alpha-administered groups were significantly higher than those in the control (nonadministered) group. This was especially noted in early phases (days 10 and 17) of antibody production when the levels of antibody in serum from the IFN-alpha-administration groups were equivalent to those of the nontolerance group. Altogether, it is suggested that oral use of IFN-alpha can elicit immunomodulating actions (e.g., antibody levels) by affecting the systemic immune system(s).

2',5'-Oligoadenylate Synthetase↗

PubMed1999

Interleukin-18 acts as an angiogenesis and tumor suppressor.

Interleukin-18 (IL-18), also called interferon-gamma (IFN-gamma)-inducing factor, has recently been characterized as a potent IFN-gamma-inducing cytokine. We now report that IL-18 is a novel antiangiogenic and antitumor cytokine. In vitro, IL-18 specifically inhibits fibroblast growth factor-2-stimulated proliferation of capillary endothelial cells. In vivo, IL-18 is sufficiently potent to suppress the fibroblast growth factor-induced corneal neovascularization by systemic administration in mice. This cytokine also inhibits embryonic angiogenesis in the chick chorioallantoic membrane assay. Systemic and intralesional administrations of IL-18 produce a significant suppression of the growth of murine T241 fibrosarcoma in syngeneic C57Bl6/J and immunodeficient SCID mice. The antitumor effect appears to be potent because an average of >75% inhibition of primary tumor growth was observed at a dose of 50 microg/kg/day. In cell culture, murine T241 fibrosarcoma cells are insensitive to recombinant IL-18 at concentrations that significantly inhibit endothelial cell proliferation. Immunohistochemical studies of tumor tissues reveal hypovascularization of the IL-18-treated tumors. These results suggest that IL-18 may participate in the regulation of a switch of tumor angiogenesis.-Cao, R., Farnebo, J., Kurimoto, M., Cao, Y. Interleukin-18 acts as an angiogenesis and tumor suppressor.

Animals↗

PubMed1999

Interleukin 18 contributes to host resistance and gamma interferon production in mice infected with virulent Salmonella typhimurium.

Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with recombinant gamma interferon (rIFN-gamma) enhanced IL-18 production. A/J mice treated in vivo with anti-IL-18 antibodies showed impaired resistance to infection, with increased bacterial loads in the liver and spleen. Administration of rIL-18 could protect A/J mice from challenge with a lethal dose of virulent salmonellae, with a dramatic reduction in bacterial numbers in the tissues. rIL-18 administration did not ameliorate the disease in IFN-gamma-R-/- mice. IL-18 proved to be required for IFN-gamma production by mouse splenocytes from conventional, scid, and rag-1(-/-) mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-gamma levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and probably acts via IFN-gamma.

Animals↗

PubMed1999

Interleukin-18 protects mice against acute herpes simplex virus type 1 infection.

We examined the effects of interleukin-18 (IL-18) in a mouse model of acute intraperitoneal infection with herpes simplex virus type 1 (HSV-1). Four days of treatment with IL-18 (from 2 days before infection to 1 day after infection) improved the survival rate of BALB/c, BALB/c nude, and BALB/c SCID mice, suggesting innate immunity. One day after infection, HSV-1 titers were higher in the peritoneal washing fluid of control BALB/c mice than in that of IL-18-treated mice. A genetic deficiency of gamma interferon (IFN-gamma), however, diminished the survival rate and the inhibition of HSV-1 growth at the injection site in the mice. Anti-asialo GM1 treatment had no influence on the protective effect of IL-18 in infected mice. IL-18 augmented IFN-gamma release in vitro by peritoneal cells from uninfected mice, while no appreciable IFN-gamma production was found in uninfected mice administered IL-18. Although IFN-gamma has the ability to induce nitric oxide (NO) production by various types of cells, administration of the NO synthase inhibitor NG-monomethyl-L-arginine resulted in superficial loss of the improved survival, but there was no influence on the inhibition of HSV-1 replication at the injection site in IL-18-treated mice. Based on these results, we propose that IFN-gamma produced before HSV-1 infection plays a key role as one of the IL-18-promoted protection mechanisms and that neither NK cells nor NO plays this role.

Acute Disease↗

PubMed1999

Interleukin-18 enhances antigen-induced eosinophil recruitment into the mouse airways.

Interleukin-18 (IL-18) has recently been identified as an IFN-gamma-inducing factor. Previous studies have shown that CD4(+) T cells, IL-5, and TNF-alpha mediate, but IFN-gamma and IL-12 (via IFN-gamma production) inhibit antigen-induced eosinophil recruitment into the airways of sensitized mice. Here, we showed that the administration of recombinant murine IL-18 enhanced antigen-induced eosinophil recruitment into the trachea and bronchoalveolar lavage fluids (BALF) of sensitized mice in a dose-dependent manner. The administration of IL-18 enhanced antigen-induced IFN-gamma and TNF-alpha production, but not IL-5 production, in the BALF and lungs of sensitized mice. Neutralizing antibody against TNF-alpha prevented antigen-induced eosinophil recruitment into the BALF of sensitized mice. Although IL-18 enhanced antigen-induced airway eosinophilia, IL-18 did not affect antigen-induced airway hyperresponsiveness in sensitized mice. These results indicate that IL-18, unlike IFN-gamma and IL-12, enhances antigen-induced eosinophil recruitment into the airways in part by increasing antigen-induced TNF-alpha production of sensitized animals. These findings suggest that IL-18 may contribute to the development and exacerbation of airway inflammation in asthma.

Analysis of Variance↗

PubMed1999

Cloning and sequencing of the beta-fructofuranosidase gene from Bacillus sp. V230.

The beta-fructofuranosidase gene (bff) from Bacillus sp. V230 has been cloned in Escherichia coli and its nucleotide sequence has been analyzed. The product of bff consists of a signal sequence of 32 amino acid (a.a.) residues for secretion and 455 a.a. residues of the extracellular beta-fructofuranosidase. The a.a. sequence of the bff product has similarities with those of the Bacillus subtilis levanscrase (63.7% identity), the Streptococcus mutans fructosyltransferase (33.7%), and the Zymomonas mobilis levanscrase and beta-fructofuranosidase (15%).

Amino Acid Sequence↗

PubMed1999

Endoscopic aqueductal plasty via the fourth ventricle through the cerebellar hemisphere under navigating system guidance--technical note.

A 1-year 8-month-old boy presented with isolated fourth ventricle after ventriculoperitoneal shunting for hydrocephalus associated with ventricular and subarachnoid hemorrhage. The therapeutic endoscope was inserted through the thin left cerebellar hemisphere. Endoscopic aqueductal plasty was performed via the enlarged fourth ventricle under guidance from a navigating system. Endoscopic aqueductal plasty via the fourth ventricle under navigating system guidance is a useful procedure enabling less invasive surgery for isolated fourth ventricle associated with slit-like ventricle after shunt placement.

Cerebellum↗

PubMed1999

Suboccipital meningocele presenting as a huge retropharyngeal mass in a patient with neurofibromatosis Type 1. Case report.

The authors report an extremely rare case of neurofibromatosis Type 1 (NF1) with a suboccipital meningocele presenting as a huge retropharyngeal mass. A 73-year-old woman with typical cutaneous manifestations of NF1 presented with nasal obstruction and dysphagia due to a retropharyngeal mass. Magnetic resonance imaging revealed a huge mass lesion extending from the right occipital bone defect to the retropharynx through the right paravertebral region. Computerized tomography scanning after intrathecal administration of contrast material confirmed that the mass was a meningocele protruding through a right occipital bone defect. The authors attempted to ligate this meningocele, most of which was excised via a suboccipital approach, but a second transcervical operation was required. Finally, the meningocele resolved and the patient was discharged without symptoms.

Aged↗

PubMed1999

Involvement of galectin-3 expression in colorectal cancer progression and metastasis.

Galectin-3 is a beta-galactoside-specific lectin that binds to laminin sugar-sites and is involved in tumor malignancy. Galectin-3 expression in relation to primary tumor and liver metastasis of colorectal cancer was examined to determined its involvement in cancer progression and metastasis. Immunohistochemical staining of galectin-3 was performed on 117 primary lesions and 15 liver metastases of colorectal cancer using TIB166 monoclonal antibody. The expression of galectin-3 was evaluated by grading the intensity of the staining as either negative, weakly positive, or strongly positive. Normal mucosa of all patients were strongly positive for galectin-3, but the staining in these tissues was still significantly less than in the primary lesions of the cancer (31.6%). Galectin-3 expression in the primary lesions was significantly increased, correlating with the progression of clinical stage (p=0. 0224), liver metastasis (p<0.0001), venous invasion (p=0.0048), and lymph node metastasis (p=0.0289). Liver metastatic lesions also showed up-regulated levels of galectin-3 compared to the primary lesions (p=0.0030). The group showing strongly positive galectin-3 had a significantly poorer prognosis than the negative/weakly positive group in terms of disease-free survival (p=0.0224). The strong expression of galectin-3 in colorectal cancer correlates with cancer progression, liver metastasis, and poor prognosis for patients.

Adenocarcinoma↗

PubMed1999

[Inhibition of antigen-specific T helper type 2 responses by Perilla frutescens extract].

Perilla frutescens leaf extract (PFE) is known as a natural medicine with anti-allergic activities, although its mechanism of action remains unclear. In this study, we examined the effect of PFE on antigen-specific antibody and on cytokine production. Mice were immunized three times (weekly) with sugi basic protein (SBP), a major allergen of Japanese cedar pollen, in alum adjuvant. PFE was injected intraperitoneally into mice on day 2 before and on the day of each immunization with SBP in alum adjuvant. Serum anti-SBP IgE and IgG 1 antibody levels were significantly suppressed in mice injected with PFE. Furthermore, the production of interleukin (IL)-4, IL-5 and IL-10 by SBP-stimulated splenocyses also decreased in PFE-injected mice in a dose-dependent manner. However, PFE had no effect on either the serum anti-SBP IgG 2 a antibody levels or on interferon (INF)-gamma production by splenocytes. When splenocytes were stimulated with concanavalin A, there was no difference in cytokine production between mice injected with PFE and control mice injected with vehicle. SBP-specific T cell line established in the presence of PFE from the lymph node cells of mice immunized with SBP showed reduced IL-4, IL-5 and IL-10 production compared with that established in the absence of PFE. In contrast, comparable levels of IFN-gamma production were observed between these two T cell lines. These data suggest that PFE down-regulates Th 2-type cytokine production and prevents the Th 1/Th 2 balance from polarizing toward Th 2-type immune responses.

Animals↗

PubMed1998

Constitutive and induced IL-18 receptor expression by various peripheral blood cell subsets as determined by anti-hIL-18R monoclonal antibody.

Interleukin-18 (IL-18) was identified as a molecule that induces IFN-gamma production and enhances NK cell cytotoxicity. Characterization of the receptor for human IL-18 (hIL-18R) is important for investigating the physiological role of IL-18 in nature. In the present study, we describe a monoclonal antibody (mAb) against hIL-18R (mAb No. 117-10C). This mAb inhibited the binding of 125I-labeled hIL-18 to IL-18R-expressing L428 cells. This mAb also neutralized hIL-18-induced T helper 1 type cytokine (IFN-gamma and GM-CSF) production by Con A-stimulated PBMC. PBMC were examined for the expression of IL-18R by two-color flow cytometry. Most CD19(+) B cells and a percentage of CD8(+) T cells were found to constitutively express IL-18R. Treatment of PBMC with IL-12 preferentially induced IL-18R expression on CD56(+) NK cells regardless of costimulation with mitogen. IL-18R expression on CD4(+) T cells was induced weakly by IL-12 treatment and moderately by PHA stimulation. However, neither could IL-12 treatment nor PHA stimulation induce IL-18R expression on CD8(+) T cells. Costimulation with both IL-12 and PHA was necessary for optimal IL-18R expression on CD8(+) T cells as well as on CD56(+) NK cells, CD4(+) T cells, and CD19(+) B cells. These results support the growing number of reports showing that IL-18 has modulatory effects on T, B, and NK cells.

Animals↗

PubMed1998

Immunoregulatory roles of IL-10 in innate immunity: IL-10 inhibits macrophage production of IFN-gamma-inducing factors but enhances NK cell production of IFN-gamma.

In our study of the immunoregulatory roles of IL-10 in innate immunity, nonantigenic phagocytosable chitin particles were administered i.v. to IL-10-deficient (knockout (KO)) mice or KO mice pretreated with anti-NK1.1 or anti-IFN-gamma Abs. The results established that chitin treatment of KO mice increased superoxide anion release from alveolar macrophages (Mphi) to a level much higher than that in wild-type (WT) mice. The results also suggested that the NK cell is the source of IFN-gamma that is primarily responsible for this alveolar Mphi priming. To further study the roles of IL-10-inhibiting chitin-induced IFN-gamma production, we used spleen cell cultures. The experiments showed that IL-12, IL-18, and TNF-alpha, which were produced by chitin-stimulated Mphi, contributed to the IFN-gamma-inducing activity of chitin. Our results established that exogenous IL-10 inhibited chitin-induced IFN-gamma production in spleen cell cultures from both KO and WT mice. Exogenous IL-10 also inhibited IL-12 and TNF-alpha production by chitin-stimulated Mphi. Exogenous IL-10 decreased IL-12- or IL-18-induced IFN-gamma levels in KO but not in WT NK cell cultures. However, exogenous IL-10 enhanced IFN-gamma levels when NK cells were stimulated simultaneously with both IL-12 and IL-18 in KO and WT cultures. Our in vitro data indicate that IL-10 has differential effects on chitin-induced IFN-gamma production. However, the inhibitory effects of endogenous IL-10 appear to be dominant in the chitin-induced alveolar Mphi priming response in vivo.

Animals↗

PubMed1998

Establishment of the cells useful for murine interleukin-18 bioassay by introducing murine interleukin-18 receptor cDNA into human myelomonocytic KG-1 cells.

We genetically engineered human myelomonocytic KG-I cells by introducing cDNA of murine interleukin-18 receptor (MuIL-18R) and established human cells which were capable of responding to MuIL-18. These cells expressed larger number of MuIL-18R (> 13,000 sites/cell) than intrinsic human IL-18 receptor (HuIL-18R) (< 2,500 sites/cell). And the cells responded to MuIL-18 as well as to HuIL-18 in a dose-dependent manner, and produced large amounts of interferon-gamma (IFN-gamma). We could estimate the amount of murine IL-18 based on the amounts of IFN-gamma produced by these cells. The stoichiometry was observed up to 150 ng/ml of MuIL-18. By using these cells, a large amount of MuIL-18 (448 +/- 89.2 ng/ml) was detected in sera of Propionibacterium acnes (P. acnes)/lipopolysaccharide (LPS)-treated endotoxic mice (the same conditions in which IL-18 was first identified). These cells provide us with a useful tool for determining the bioactivity of MuIL-18.

Animals↗

PubMed1998

Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN-gamma gene expression in human T cells.

T cells contribute significantly the to host's early defense against viral and bacterial infections and are essential for clearance of the pathogen. IFN-gamma, a product of activated T and NK cells, has, in addition to its direct antimicrobial activity, a major role in activating cell-mediated immunity. Here we report that cytokines secreted by influenza A virus-infected macrophages are able to induce IFN-gamma synthesis in human T cells. Influenza A virus-infected human peripheral macrophages secreted IFN-alpha/beta, TNF-alpha, IL-1beta, and a recently identified cytokine, IL-18 (or IFN-gamma-inducing factor), whereas the production of IL-12 was not detected. Supernatants collected from virus-infected macrophages induced rapid IFN-gamma mRNA expression and protein production in T cells. This was down-regulated by the addition of neutralizing anti-IFN-alpha/beta Abs, whereas neutralizing anti-IL-12 Abs had no effect on IFN-gamma gene expression. Exogenously added IFN-alpha/beta also rapidly stimulated the synthesis of IFN-gamma mRNA in T cells independently of protein synthesis. IL-18 synergized with IFN-alpha to up-regulate IFN-gamma gene expression and protein production. The data suggest that IFN-alpha/beta and IL-18 produced by macrophages during virus infection may act together to induce IFN-gamma synthesis and, consequently, may play an important role for both of these cytokines in the development of Th1-type immune responses.

Cytokines↗