Biomedical subjects

N Inagaki

Publications and source records attributed to N Inagaki.

At least 55 records · Page 3Linked to original sources

PubMed2000

Effects of luteolin and other flavonoids on IgE-mediated allergic reactions.

The anti-allergic action of luteolin was investigated in the rodent experimental allergic models. In the present study, the effects of luteolin were compared to those of baicalein, quercetin, and prednisolone. Luteolin as well as baicalein, quercetin, and prednisolone inhibited the IgE antibody-mediated biphasic cutaneous reaction (immediate phase reaction and late phase reaction) in mice. However, these compounds did not affect the histamine-, serotonin-, and platelet activating factor-induced cutaneous reactions in rats. In an in vitro study, luteolin, baicalein, and quercetin inhibited IgE-mediated histamine release from bone marrow-derived cultured murine mast cells (BMMC) and rat peritoneal mast cells. These compounds also inhibited IgE-mediated TNF-alpha and IL-6 production from BMMC. From these results, luteolin inhibited the IgE-mediated biphasic cutaneous reaction mainly by the inhibition of histamine and cytokine release from mast cells, but not through mediator antagonistic effects.

Animals↗

PubMed2000

Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in mice.

BACKGROUND: In mice that are passively sensitized to IgE, cutaneous antigen challenge produces a biphasic response with peaks at 1 and 24 hours after challenge. OBJECTIVE: We investigated the role of mast cells in the IgE-mediated late-phase reaction in mice. METHODS: We histologically and ultrastructurally investigated the morphologic changes of mast cells during the biphasic responses. RESULTS: Degranulation of mast cells, which was observed between 4 and 24 hours after challenge, reached a peak at 8 hours. Piecemeal degranulation was seen during the immediate phase reaction. The number of IL-6-positive mast cells was increased after 4 hours in both IgE-sensitized and unsensitized mice, but positive cells showed a greater increase in sensitized mice and reached a peak after 8 hours. With in situ hybridization experiments, mast cells were positive for IL-6 messenger RNA at 6 hours after challenge. CONCLUSION: These findings indicate that anaphylactic degranulation of mast cells and the expression of IL-6 mRNA within 4 hours after antigen challenge are important for the onset of the late-phase allergic cutaneous reaction in mice.

Animals↗

PubMed2000

Effect of Am-80, a retinoid derivative, on 2, 4-dinitrofluorobenzene-induced contact dermatitis in mice.

Retinoids have many pharmacological activities, including anti-inflammatory action and antiangiogenesis, effected through the regulation of various gene transcriptions. In this study, we investigated the effect of Am-80, one of the retinoic acid derivatives, on hapten-induced contact hypersensitivity in BALB/c mice. After application of 2,4-dinitrofluorobenzene (DNFB) to the ears of the mice, severe contact hypersensitivity with marked infiltration of inflammatory cells and hypertrophy of the epidermis was caused. The thickness of the ears increased biphasically and reached a peak 3 and 24 h after the DNFB challenge. Am-80 significantly inhibited ear thickness in the late-(24 h), but not the early-phase (3 h) reaction in a dose-dependent manner. In a histopathological study, obvious depression of edema and infiltration of inflammatory cells was observed in the ears of mice treated with Am-80. Am-80 inhibited the levels of expression in mice ears of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6), but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). Furthermore, Am-80 inhibited the antigen-induced production of some cytokines, including IFN-gamma and IL-6, but not IL-4, in vitro. Therefore, Am-80 inhibited hapten-induced contact hypersensitivity through the direct inhibition of inflammatory cytokines such as IFN-gamma and IL-6.

Animals↗

PubMed2000

Effect of a novel anti-allergic agent, HSR-609, on antigen-induced airway hyperresponsiveness in mice.

The effects of a newly synthesized anti-allergic agent, HSR-609, on allergic airway hyperresponsiveness and airway inflammation have been studied in sensitized mice. The effects were compared with those of two histamine H(1) receptor antagonists, cetirizine and terfenadine, and prednisolone. Three inhalations of antigen caused an increase in leukocytes (including eosinophils) with increases in IL-5 in BALF and airway hyperresponsiveness to acetylcholine in BALB/c mice. All drugs were orally administered once a day for 10 days from the day before the first inhalation of antigen. HSR-609 (10 mg/kg) and prednisolone (5 mg/kg) significantly inhibited the antigen-induced airway hyperresponsiveness, whereas cetirizine (10 mg/kg) or terfenadine (100 mg/kg) did not affect this airway response. At the same time HSR-609 inhibited the antigen-induced eosinophilia and IL-5 production in BALF. Prednisolone also showed an inhibitory effect on the airway eosinophilia and IL-5 production but not cetirizine and terfenadine in the same experiments. In addition, HSR-609 (p.o.) dose-dependently suppressed the accumulation of eosinophils elicited by antigen-stimulated D10G4.1 cells, a murine Th2 clone, in peritoneal cavity lavage fluid in AKR/J mice. These results suggest that HSR-609 inhibits allergic airway hyperresponsiveness to acetylcholine probably because of the inhibition of Th2-dependent eosinophilia caused by IL-5. In addition, effects of HSR-609 were different from those of cetirizine and terfenadine concerning the inhibition of antigen-induced airway hyperresponsiveness in mice.

Acetylcholine↗

PubMed2000

Inhibition of passive cutaneous anaphylaxis-associated scratching behavior by mu-opioid receptor antagonists in ICR mice.

BACKGROUND: Itching in humans is attenuated by mu-opioid receptor antagonists. ICR mice display increases in scratching behavior upon induction of IgE-mediated passive cutaneous anaphylaxis (PCA), or intradermal injection of compound 48/80 or histamine. METHODS: Cutaneous reactions were induced in ICR mice by IgE-mediated PCA, compound 48/80 and histamine, and the scratching behavior associated with the cutaneous reactions was evaluated. RESULTS: Naloxone and nalmefene reduced the incidence of scratching behavior associated with PCA. Naloxone also inhibited the induction of scratching behavior caused by compound 48/80 and histamine. Naloxone did not affect the increase in vascular permeability caused by PCA and injection of compound 48/80. CONCLUSION: Scratching behavior in mice may be induced by a sensation or a mechanism similar to itching in humans and should become a useful model for examining itching in humans.

Animals↗

PubMed1999

Troglitazone but not pioglitazone affects ATP-sensitive K(+) channel activity.

We compared the effects of the two thiazolidinedione derivatives, troglitazone and pioglitazone, on ATP-sensitive K(+) (K(ATP)) channel activities. Pancreatic beta-cell type and cardiac type K(ATP) channels were reconstituted in COS-1 cells (SV 40-transformed African green monkey kidney (AGMK) cells) by heterologously expressing sulfonylurea receptor 1 (SUR1) plus Kir6.2 and sulfonylurea receptor 2A (SUR2A) plus Kir6.2, respectively. Troglitazone inhibited [86Rb(+)] efflux in both K(ATP) channel types in the presence of metabolic inhibitors, which was confirmed by electrophysiological techniques. The [86Rb(+)] efflux increased by the channel openers diazoxide and pinacidil was abolished by troglitazone. In contrast, pioglitazone did not affect these channel activities in either type K(ATP) channel. These results suggest that troglitazone modulates the various cellular functions including insulin secretion by inhibiting the K(ATP) channels, while pioglitazone has no effect on K(ATP) channel activity.

ATP-Binding Cassette Transporters↗

PubMed1999

Ca2+ and protein kinase C signaling for histamine and sulfidoleukotrienes released from human cultured mast cells.

Human cultured mast cells (HCMC) release histamine and sulfidoleukotrienes (LTs) upon IgE-FcepsilonRI-mediated mast cell activation. We analyzed the Ca2+ and PKC signaling in HCMC and compared it to that in rodent mast cells. In HCMC, after IgE-mediated stimulation, an elevation of [Ca2+]i and PKC translocation to the membrane fraction was observed. As concerns Ca2+ signaling, 1) IgE-mediated histamine and LTs release was abolished after Ca2+ depletion, and the reconstitution of Ca2+ recovered the release of histamine and LTs. As regards PKC signaling, 1) staurosporine inhibited IgE-mediated mediator release. 2) PKC-downregulated mast cells did not release histamine and LTs. A23187 and PMA synergistically potentiated the activation of extracellular-regulated kinase and synergistically induced histamine and LTs release. These results demonstrated that HCMC might be useful for analysis of the signal transduction pathway for mediator release, such as histamine and LTs.

Animals↗

PubMed1999

Terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase.

Bruton's tyrosine kinase (Btk) plays pivotal roles in mast cell activation as well as in B cell development. Btk mutations lead to severe impairments in proinflammatory cytokine production induced by cross-linking of high-affinity IgE receptor on mast cells. By using an in vitro assay to measure the activity that blocks the interaction between protein kinase C and the pleckstrin homology domain of Btk, terreic acid (TA) was identified and characterized in this study. This quinone epoxide specifically inhibited the enzymatic activity of Btk in mast cells and cell-free assays. TA faithfully recapitulated the phenotypic defects of btk mutant mast cells in high-affinity IgE receptor-stimulated wild-type mast cells without affecting the enzymatic activities and expressions of many other signaling molecules, including those of protein kinase C. Therefore, this study confirmed the important roles of Btk in mast cell functions and showed the usefulness of TA in probing into the functions of Btk in mast cells and other immune cell systems. Another insight obtained from this study is that the screening method used to identify TA is a useful approach to finding more efficacious Btk inhibitors.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed1999

Participation of histamine H1 and H2 receptors in passive cutaneous anaphylaxis-induced scratching behavior in ICR mice.

Scratching behavior associated with passive cutaneous anaphylaxis was examined and compared to that induced by compound 48/80 or histamine in ICR mice. Elicitation of passive cutaneous anaphylaxis, and intradermal injections of compound 48/80, histamine or serotonin induced both scratching behavior and vascular permeability increase in ICR mice. In mast cell-deficient WBB6F1-W/Wv mice, although histamine induced scratching behavior and vascular permeability increase, passive cutaneous anaphylaxis was not observed. Cetirizine and terfenadine significantly inhibited the scratching behavior and vascular permeability increase caused by passive cutaneous anaphylaxis, compound 48/80 and histamine. The histamine H1 receptor antagonists inhibited the vascular permeability increase almost completely, whereas they failed to abolish the scratching behavior. Famotidine and ranitidine significantly inhibited the scratching behavior caused by histamine. The histamine H2 receptor antagonists did not affect the vascular permeability increase caused by histamine. The combination of cetirizine and ranitidine abolished the histamine-induced scratching behavior. The combination, however, failed to potentiate the inhibition of passive cutaneous anaphylaxis-induced scratching behavior significantly. The results indicated that histamine induces scratching behavior in ICR mice through both histamine H1 and H2 receptors, and that histamine plays a major role in passive cutaneous anaphylaxis-induced scratching behavior. Histamine might also play an important role in compound 48/80-induced scratching behavior.

Animals↗

PubMed1999

Immuno-localization of sulphonylurea receptor 1 in rat pancreas.

AIMS/HYPOTHESIS: A sulphonylurea receptor, SUR1, and an inward rectifier potassium channel, Kir6.2, reconstitute the ATP-sensitive K(+) channel that mediates glucose-induced insulin secretion in pancreatic beta cells. We reported previously that Kir6.2 were localized at insulin-, glucagon-, and somatostatin-producing cells. In this new study we aimed to determine the distribution of SUR1 in rat pancreatic islets and to suggest the location of the ATP-sensitive K(+) channels in the islet. METHODS: Western blot analysis was carried out using two anti-SUR1 antibodies, which had been raised against different portions of rat SUR1. SUR1, Kir 6.2, and islet hormones were then localized by indirect immunofluorescence staining of the cryosections of rat pancreas. RESULTS: In Western blot analysis, each of the anti-SUR1 antibodies detected a band at 140 kDa, which is close to the predicted molecular weight of SUR1, in the homogenate of isolated pancreatic islets. Double immunofluorescence staining of cryosections showed that SUR1 occurred all over the islets, and that SUR1 colocalized with insulin, glucagon, somatostatin, and pancreatic polypeptide. Kir6.2 was also shown to be present in pancreatic polypeptide cells. CONCLUSION/INTERPRETATION: Together with our previously reported data, the above findings indicate that K(ATP) channels comprising SUR1 and Kir6.2 occur not only in beta cells but also in the alpha, delta, and pancreatic polypeptide cells of the pancreatic islets, suggesting that therapeutic sulphonylureas could act on these cells directly. [Diabetologia (1999) 42: 1204-1211]

ATP-Binding Cassette Transporters↗

PubMed1999

Hysteroscopic selective salpingography.

OBJECTIVE: To evaluate the effectiveness of hysteroscopic selective salpingography (HSS) as a method for diagnosing the tubal proximal occlusion shown by hysterosalpingography (HSG). DESIGN: Prospective study. SETTING: Outpatient Department of Obstetrics and Gynecology, Social Insurance Saitama Chuo Hospital, Urawa, Japan. PATIENT(S): A total of 572 infertile women underwent HSG. Forty-seven of 50 women with unilateral or bilateral proximal tubal occlusion demonstrated by HSG underwent HSS. INTERVENTION(S): Hysteroscopic selective salpingography was performed for the diagnosis of tubal occlusion in cases in which the proximal tubal occlusion was shown by HSG. MAIN OUTCOME MEASURE(S): Number of patients who underwent HSS and pregnancy rate after HSS. RESULT(S): Twenty-seven (79.4%) of 34 patients with unilateral occlusion diagnosed by HSG were shown to have normal patency by HSS. Of 12 women with bilaterally normal patent tubes confirmed by HSS, 8 (66.7%) achieved normal pregnancies within 1 year. Seven (53.8%) of 13 patients with bilateral occlusion found by HSG were shown to have normally patent tubes by HSS. CONCLUSION: The simple method of HSS was clinically effective for evaluating the presence of proximal tubal occlusion.

Adult↗

PubMed1999

Role of cyclic 3',5'-adenosine monophosphate in the regulation of chemical mediator release and cytokine production from cultured human mast cells.

BACKGROUND: Cultured human mast cells are known to resemble human lung mast cells in terms of the profiles of intracellular protease, the characteristics of histamine release, and the pharmacologic properties. OBJECTIVE: The role of cyclic 3',5'-adenosine monophosphate (cAMP) in chemical mediator release and cytokine production by human mast cells was determined. METHODS: We investigated the effects of cAMP-elevating agents on IgE-mediated chemical mediator release and cytokine production by cultured human mast cells. We also examined the relationship between intracellular cAMP levels and the inhibition of chemical mediator release or cytokine production by various drugs. RESULTS: beta-agonists significantly suppressed IgE-mediated release of histamine, leukotrienes, and PGD2 (chemical mediators) and the production of GM-CSF, IL-5 and macrophage inflammatory protein-1alpha (cytokines). Phosphodiesterase inhibitors (theophylline, rolipram, and cilostazol) had no effect on chemical mediators but suppressed cytokine production. Dibutyryl cAMP significantly suppressed both chemical mediator release and cytokine production, suggesting that their induction was regulated by intracellular cAMP. Elevation of cAMP by beta-agonists at 10 minutes after treatment correlated well with the inhibition of histamine release. There was a significant relationship between cAMP elevation at 180 minutes and the inhibition of GM-CSF production at 360 minutes by beta-agonists, rolipram, or cilostazol. Although 100 micromol/L theophylline significantly inhibited GM-CSF production, it had no effect on cAMP. CONCLUSION: Elevation of cAMP may be responsible for the inhibitory effect of beta-agonists, rolipram, and cilostazol on chemical mediator release and cytokine production by cultured human mast cells. In contrast, theophylline may inhibit GM-CSF production independently of cAMP.

Adrenergic beta-Agonists↗

PubMed1999

Phospholipase C-gamma and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance.

Expression of rat TrkA in Xenopus spinal neurons confers responsiveness of these neurons to nerve growth factor (NGF) in assays of neuronal survival and growth cone chemotropism. Mutational analysis indicates that coactivation of phospholipase C-gamma (PLC-gamma) and phosphoinositide 3-kinase (PI3-kinase) by specific cytoplasmic domains of TrkA is essential for triggering chemoattraction of the growth cone in an NGF gradient. Uniform exposure of TrkA-expressing neurons to NGF resulted in a cross-desensitization of turning responses induced by a gradient of netrin-1, brain-derived neurotrophic factor (BDNF), or myelin-associated glycoprotein (MAG) but not by a gradient of collapsin-1/semaphorin III/D or neurotrophin-3 (NT-3). These results, together with the effects of pharmacological inhibitors, support the notion that there are common cytosolic signaling pathways for two separate groups of guidance cues, one of which requires coactivation of PLC-gamma and PI3-kinase pathways.

Animals↗

PubMed1999

Gestational choriocarcinoma whose responsible pregnancy was a complete hydatidiform mole identified by PCR analysis with new sequence tagged site primers.

We report a case where the pregnancy responsible for a gestational choriocarcinoma was not the antecedent pregnancy or the second normal term delivery, but a complete hydatidiform mole that had advanced to clinically invasive mole. This responsible pregnancy was identified by polymerase chain reaction analysis (PCR). PCR analysis was performed by using five new sets of sequence-tagged site (STS) primers on four chromosomes (chr. 1, D1S225; chr. 3, D3S1744; chr. 12, D12S1090; chr. 18, D18S849 and D18S877). The constitution of alleles of choriocarcinoma was shown to be almost identical with that of the husband on every marker. The allele patterns of choriocarcinoma on D3S1744 and D12S1090 were not observed with DNA from the patient. The band pattern originating from molar DNA was also identical with those of the husband and choriocarcinomas on D18S849 and D1S225.

Choriocarcinoma↗

PubMed1999

Synthesis of benzimidazole derivatives as antiallergic agents with 5-lipoxygenase inhibiting action.

Syntheses were conducted of novel benzimidazole derivatives that suppress histamine release from mast cells, inhibit 5-lipoxygenase, and possess antioxidative action. Among the compounds synthesized, 1-[2-[2-(4-hydroxy- 2,3,5-trimethylphenoxy)ethoxy]ethyl]-2-(4-methyl-1- homopiperazino)benzimidazole (22) potently suppressed histamine release from rat peritoneal mast cells triggered by the antigen-antibody reaction, inhibited 5-lipoxygenase in rat basophilic leukemia-1 (RBL-1) cells, and prevented the NADPH-dependent lipid peroxidation induced by Fe(3+)-ADP in rat liver microsomes, in addition to an antagonizing the contraction of guinea pig ileum caused by histamine.

Animals↗

PubMed1999

Synthesis of trimethylhydroquinone derivatives as anti-allergic agents with anti-oxidative actions.

A novel series of trimethylhydroquinone derivatives was synthesized and evaluated for their anti-lipid peroxidation activity in rat liver microsomes, inhibition of rat basophilic leukemia-1 (RBL-1) cell 5-lipoxygenase and 48 h homologous passive cutaneous anaphylaxis (PCA) activity in rats. 4-[4-[4-(Diphenylmethyl)-1-piperazinyl]-butoxy]-2,3,6-trimethyl phenol (9c) exhibited the ability to inhibit Fe(3+)-ADP induced NADPH dependent lipid peroxidation (IC50 = 5.3 x 10(-7) M), 5-lipoxygenase ((IC50 = 3.5 x 10(-7) M) and PCA reaction (57% inhibition at 100 mg/kg p.o.).

Administration, Oral↗

PubMed1999

IPD-1151T (suplatast tosilate) inhibits interleukin (IL)-13 release but not IL-4 release from basophils.

The effect of suplatast tosilate (IPD-1151T), which is known to suppress interleukin (IL)-4 release from T cells, on the release of IL-4 and IL-13 from human peripheral basophils was investigated. Basophils were obtained from 16 mite-sensitive atopic asthmatic patients. IPD-1151T clearly inhibited the antigen-induced release of IL-13 but not IL-4. These results suggest that IPD-1151T possesses different activity for the regulation of cytokine release in basophils and T cells.

Adult↗

PubMed1999

Effect of overproduction of interleukin 5 on dinitrofluorobenzene-induced allergic cutaneous response in mice.

The effect of overproduction of interleukin (IL) 5 on the allergic cutaneous response was investigated in transgenic mice overexpressing IL-5. Five repeated topical applications of 2, 4-dinitrofluorobenzene (DNFB) to the ears of mice resulted in allergic dermatitis on the ears as well as significant elevation in dinitrophenol-specific IgE antibody and total IgE in the serum in both wild-type and transgenic mice. The development of dermatitis as measured by skin thickness and histopathological changes were potentiated in the transgenic mice. In IL-5 transgenic mice, significant accumulation of eosinophils in skin lesions was observed after five paintings of DNFB, and the magnitudes of eosinophilia and IL-5 messenger RNA expression were significantly higher than in wild-type mice. The dinitrophenol-specific and total IgE in the serum were higher in IL-5 transgenic mice. The late phase reaction of IgE antibody-mediated biphasic cutaneous response was potentiated in IL-5 transgenic mice. The magnitudes of vasopermeability increase by passive cutaneous anaphylaxis, serotonin, and platelet-activating factor were similar in both mice. These results indicate that overproduction of IL-5 resulted in the potentiation of DNFB-induced dermatitis by elevation of IgE production, IgE-mediated allergic late-phase cutaneous reaction, and eosinophilia in the skin lesion.

Animals↗