PubMed Health⌕ Search

Biomedical subjects

T Hisamitsu

Publications and source records attributed to T Hisamitsu.

At least 19 recordsLinked to original sources
PubMed2004

Suppression of matrix metalloproteinase production from nasal fibroblasts by macrolide antibiotics in vitro.

It is well known that low-dose and long-term administration of macrolide antibiotics favourably modify the clinical status of chronic airway inflammatory diseases. However, the therapeutic mode of action of macrolide antibiotics is not well understood. The present study aimed to examine the influence of macrolide antibiotics, roxithromycin (RXM) and josamycin (JM) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts (NPF) in vitro. NPF, at a concentration of 2.5 x 10(5) cells x mL(-1), were stimulated with tumour necrosis factor (TNF)-alpha in the presence of various concentrations of RXM or JM for 24 h. MMP-2 and -9 levels in culture supernatants were analysed by ELISA, and MMP mRNA expression was examined by RT-PCR. The influence of RXM on nuclear factor (NF)-kappaB and activator protein (AP)-1 activation was also examined. Addition of RXM (but not JM) at 5.0 and 7.5 microg x mL(-1) significantly suppressed the production of MMP-2 and -9 from NPF induced by TNF-alpha stimulation. RXM also suppressed MMP mRNA expression through the inhibition of NF-kappaB and AP-1 activation. The present results suggest that the suppressive activity of roxithromycin on MMP-2 and -9 production is, in part, responsible for the therapeutic action of macrolides on chronic airway inflammatory diseases.

Adult↗
PubMed2001

A mechanism of Ca2+ release from Ca2+ stores coupling to the Na+/Ca2+ exchanger in cultured smooth muscle cells.

We previously observed Ca2+ release from intracellular Ca2+ stores caused by reduction in extracellular Na+ concentration ([Na+]o). The purpose of this study was to determine whether lowering [Na+]o can elicit Ca2+ release from Ca2+ stores via the Na+/Ca2+ exchanger and to elucidate the mechanisms related to the Ca2+ release pathway in cultured longitudinal smooth muscle cells obtained from guinea pig ileum. Low [Na+]o-induced Ca2+ release was inhibited by antisense oligodeoxynucleotides for Na+/Ca2+ exchanger type 1 (anti-NCX). Application of anti-NCX to cells attenuated both the number of Ca2+ responding cells and the expression of the exchanger. Moreover, microinjection of heparin, a blocker of inositol 1,4,5-trisphosphate (IP3) receptors, into the cells inhibited low [Na+]o-induced Ca2+ release. These findings suggest that low [Na+]o-induced Ca2+ release occurs through an IP3-induced Ca2+ release mechanism due to changes in the Ca2+ flux regulated by the Na+/Ca2+ exchanger.

Animals↗
PubMed2001

Enhancement of endogenous corticosterone levels by a macrolide antibiotic, roxithromycin in mice.

The influence of roxithromycin (RXM), a macrolide antibiotic, on endogenous corticosterone (CS) levels was examined in BALB/c mice. Mice were sensitized intraperitoneally with two doses of Keyhole Limpet Hemocyanin at 1 week intervals. Mice were given orally 2.5 mg/kg RXM once a day for 14 days starting 7 days after the first sensitization. RXM administration caused markedly increase in endogenous plasma CS levels which was peaked at 60 min after the administration. However, josamycin did not influence on endogenous CS levels in plasma. Injection of dexamethasone inhibits the plasma CS hyperproduction induced by RXM treatment.

Allergens↗
PubMed2001

The inhibitory effect of serotonin on the spontaneous discharge of suprachiasmatic neurons in hypothalamic slice is mediated by 5-HT(7) receptor.

The effects of serotonin (5-HT) receptor agonists and antagonists on the spontaneous discharge of suprachiasmatic nucleus (SCN) neurons were investigated using rat hypothalamic slice. It was found that: (1) the SCN neurons showed a persistent rhythm in the spontaneous discharge rate, which was higher during the light phase than during the dark phase; (2) the effects of 5-HT on SCN neurons was inhibitory in nature and the sensitivity of SCN neurons to 5-HT during the light phase was lower than that during the dark phase; (3) both 5-HT and 5-HT(1/7) receptor agonist, (+/-)-8-hydroxy-2-(DL-N-propylamino) tetralin hydrobromide, could inhibit the spontaneous discharge of SCN neurons. This inhibitory effect could be blocked by 5-HT(2/7) receptor antagonist ritanserin and putative 5-HT(7) receptor antagonists clozapine, but neither by selective 5-HT(2) receptor antagonist ketanserin, nor by 5-HT(1) receptor antagonist pindolol. It was suggested that the inhibitory effect of 5-HT on the spontaneous discharge of SCN neurons in rat hypothalamic slice is mediated by 5-HT(7) receptor subtype.

Animals↗
PubMed2001

Modulation of Th2 type cytokine production from human peripheral blood leukocytes by a macrolide antibiotic, roxithromycin, in vitro.

The influence of a macrolide antibiotic, roxithromycin (RXM), on Th1 and Th2 cytokine productions from human peripheral blood T cells was examined under stimulation with co-stimulatory molecules. Peripheral blood T cells prepared from both healthy and allergic rhinitis donors were cultured in the presence of RXM on anti-CD3 mAb and anti-CD26 mAb-coated wells, anti-CD3 mAb and anti-CD28 mAb-coated wells, and anti-CD3 and PMA. T-cell proliferation, along with the concentration of interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-5 were measured. RXM did not affect T-cell proliferation induced by several ways of co-stimulatory activation as assessed by 3H-thymidine incorporation into DNA. RXM also had no effect on IL-2 and IFN-gamma secretion by T cells prepared from both healthy and allergic rhinitis donors. On the other hand, RXM markedly inhibited both IL-4 and IL-5 secretions under each of the co-stimulatory conditions in a dose-dependent manner. These results indicate that RXM inhibits specifically Th2 cytokine secretion from T cells induced by co-stimulatory molecule stimulations. This inhibitory action of RXM may be partially responsible for attenuating effect of the agent on the inflammatory diseases.

Adult↗
PubMed2001

Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro.

BACKGROUND: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood. AIM: The present study was designed to examine the influence of macrolide antibiotics on effector cell functions responsible for inflammation through the choice of roxithromycin (RXM) and mast cell. METHODS: Mast cells were induced by long-term culture of splenocytes from BALB/c mice. RXM was added to the cultures at seeding and then every 4-5 days, when the culture medium was replaced with a fresh one. The influence of RXM on mast cell growth was evaluated by counting the number of cells grown on the 16th day. We also examined the influence of RXM on mast cell activation by examining histamine release and inflammatory cytokine secretion. RESULTS AND CONCLUSION: RXM could not inhibit mast cell growth, even when splenocytes were exposed to 100 microg/ml of RXM throughout the entire culture periods. RXM also could not suppress histamine release from cultured mast cells in response to non-immunological and immunological stimulations. However, RXM could suppress inflammatory cytokine, interleukin-1beta, interleukin-6, granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha, secretions induced by concanavalin A stimulation at a concentration of as little as 0.5 microg/ml. These results may suggest that RXM modulated the ability of mast cells to secrete inflammatory cytokines and results in improvement of clinical condition of chronic inflammatory diseases.

Animals↗
PubMed2001

[Effectiveness of Saiko-Keishi-To (TJ-10, a Kampo herbal medicine) for trigeminal neuralgia in rats].

It is known that Saiko-Keishi-To (TJ-10), a Kampo herbal medicine used for the treatment of epilepsy, shows a satisfactory curative effect even in the patients suffering from trigeminal neuralgia. To verify the effectiveness of TJ-10, Wistar rats with chronic neuralgia of the mandibular nerve were prepared and TJ-10 was administered to them for 4 weeks following the manifestation of pain in the mandibular region. The result reveals that the rise in the pain threshold in the mandibular region is more significant in the rats administered TJ-10 than in those in the control group. However, in the tail flick test, no significant change was observed in the pain threshold. These findings suggest that TJ-10 is effective for controlling the manifestation of pain in ligatured nerves, by local effect, not by general analgesic effect.

Analgesics↗
PubMed2001

Analgesic effect of endomorphin-1.

AIM: To study the analgesic effect of endomorphin-1 (EM-1). METHODS: The experiment was performed in rats and mice to study the analgesic effect of intraperitoneal (ip) injection of EM-1 with tail stimulation-vocalization test, writhing test, adjuvant arthritis, and neuropathic pain model and to compare it with the analgesic effects produced by intracerebroventricular (icv) and intrathecal (it) administrations. RESULTS: 1) EM-1 raised the pain threshold dose-dependently in tail stimulation-vocalization test in rats and inhibited the writhing responses induced by ip acetic acid in mice. EM-1 also decreased the hyperalgesia in both adjuvant arthritis and neuropathic pain model. 2) The analgesic effect induced by central (icv and it) administration of EM-1 was faster and more powerful than that induced by peripheral (ip) administration. 3) The analgesic effect of EM-1 was reversed by naloxone (opioid receptor antagonist), as well as by cyprodime (mu-opioid receptor selective antagonist). Repeated administrations of EM-1 induced tolerance. CONCLUSION: EM-1 had a definite analgesic effect and the analgesic effect of EM-1 was mediated by central mu-opioid receptor.

Analgesics, Opioid↗
PubMed2000

Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro.

The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 microg/ml haemocyanin and various concentrations of the agents. Low concentrations (<1.5 x 10(-4)M) of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 x 10(-4) M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 x 10(-4) M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 x 10(-4)M of the agents and the expression of molecules were examined by flow cytometer 24h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro.

Animals↗
PubMed2000

The inhibitory effect of anti-allergic agent suplatast tosilate (IPD-1151T) on methacholine- and allergen-induced bronchoconstriction in sensitized mice. asakazu@med.showa-u.dc.jp.

The influence of an anti-allergic agent, suplatast tosilate (IPD-1151T; (+/-)-[2-[4-(3-ethoxy-2-hydroxypropoxy)phenyl-carbamoyl]-ethyl] dimethylsulfonium p-toluenesulfonate) on allergic bronchoconstriction induced by allergen and methacholine (MCh) were examined in mice. BALB/c mice were sensitized by intraperitoneal injection of dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) mixed with A1(OH)3 (DNP-KLH). IPD-1151T was administered orally once a day for either 5 or 14 days in doses of 10, 30 or 100 mg/kg. Bronchoconstriction was measured 24h after the final drug administration. IPD-1151T inhibited both antigen- and MCh-mediated bronchoconstriction in actively sensitized mice. The inhibition induced was closely related to the dose and frequency of oral administration of the agent. We also examined the effect of IPD-1151T on IgE production in response to DNP-KLH immunization. IPD-1151T inhibited dose-dependently both total and specific IgE concentrations in serum prepared from mice 15 days after immunization. These results strongly indicate that IPD-1151T inhibits IgE production in vivo and results in attenuating effect on bronchoconstriction.

Allergens↗
PubMed2000

[Intracellular calcium kinetics after odorant stimulus in olfactory receptor cells isolated from mice].

cAMP and IP3 act as secondary messengers in olfactory signal transduction and when activated, stimulate calcium levels in olfactory receptor cells. Little is known however, about the causal mechanism. We studied calcium kinetics in mouse olfactory receptor cells after odorant stimuli. Olfactory receptor cells were isolated from female BALB/c mice, treted with trypsin, and stained with Fura-2/AM. Changes in intracellular Ca2+ concentrations in stained cells were measured with a fluorescent microscopic image-processing device (ARGUS-50; Hamamatsu Photonix, Japan). We found that intracellular Ca2+ concentrations rose after exposure to a set of odorants, including 3-ethoxy-4-hydroxy-benzaldehyde, caprylic acid, heptanoic acid, nonanoic acid, eugenol, phenethyl alcohol, and n-amyl acetate. Adding 2', 5'-dideoxyadenosine, a cAMP inhibitor, beforehand suppressed olfactory receptor cell response to odorants. Intracellular Ca2+ concentrations increased substantially in response to stimulation by odorants in calcium-free Ringer's solution, but only a slight increase was seen in intracellular calcium concentration in response stimulation by a high concentration of K+ (145.6 mM) in calcium-free Ringer's solution. The increase in intracellular Ca2+ concentration after odorant stimuli was suppressed when olfactory receptor cells were pretreated with ryanodine, which releases Ca2+ from intracellular stores. These findings suggest that elevated Ca2+ concentrations may be involved in releasing Ca2+ from intracellular calcium stores in mouse olfactory receptor cells, in which cAMP functions as a secondary messenger in olfactory signal transduction.

Animals↗
PubMed2000

[Splenic natural killer cell activity is suppressed by ligation of unilateral mental nerve in rats].

It has been reported that surgical procedures and postoperative pain suppress immune activities of the patient. But it is not clear if chronic pain in a small area affects immune activities. We prepared rats with chronic neuralgia of the mental branch originating from the mandibular nerve (a division of the trigeminal nerve) and examined the change of splenic NK-cell activity. Surgical procedures to prepare rat models for the study were as follows: one mental nerve was exposed and ligated at the mental foramen in order to create hypersensitivity in the ipsilateral innervated area. Splenic NK-cell activity 3 weeks after the surgery was reduced significantly in the operation group than that of the sham-operation group and the non-operated control group. The result suggests that the immune functions are remarkably affected by chronic pain evoked in a limited area such as the area innervated by the mental nerve.

Animals↗
PubMed1999

Suppressive activity of a macrolide antibiotic, roxithromycin, on pro-inflammatory cytokine production in vitro and in vivo.

This study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM), on the production of pro-inflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. In the first experiments, we examined the effect of RXM on in vitro cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes. The monocytes were cultured in the presence of various doses of the agent. After 24 h, the culture supernatants were obtained and assayed for IL-1beta and TNF-alpha contents by enzyme-linked immunosorbent assay. RXM suppressed the in vitro production of IL-1beta and TNF-alpha in response to LPS stimulation. This was dose dependent and first noted at a concentration of as little as 0.05 microg/ml, which is much lower than therapeutic blood levels. In the second part of the experiments, we examined the influence of RXM on the appearance of IL-1beta and TNF-alpha in mouse lung extract induced by LPS inhalation. RXM was administered orally into BALB/c mice at a single dose of 2.5 mg/kg once a day for 5-12 weeks. These mice were then instilled with LPS into the trachea and examined for the presence of cytokines in aqueous lung extracts. Pretreatment of mice with RXM for 5 weeks did not influence of the appearance of both IL-1beta and TNF-alpha in aqueous lung extracts. However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts.

Administration, Inhalation↗
PubMed1999

[Denervation of the cervical sympathetic nerve inhibited the splenic natural killer cell activity by modulation of the splenic sympathetic nerve activities in rats].

It is known that the splenic natural killer cell (NK) activity 4 weeks after unilateral resection of the cervical sympathetic nerve (csn) is significantly lower than that after sham operation in rats. To investigate the role of the splenic sympathetic nerve, the splenic NK activity after csn was compared in the control animals (n = 9) and the splenic sympathetic nerve denervated animals (n = 8). The splenic NK activity in control group was reduced significantly after csn, whereas that in splenic nerve denervated group did not reveal significant change after csn. The results suggest that the reduction of the splenic NK activity after csn is induced through the modulation of the splenic sympathetic nerve activities.

Animals↗
PubMed1998

Role of endogenous interferon-gamma on the enhancement of splenic NK cell activity by electroacupuncture stimulation in mice.

Successive electro-acupuncture (EA) stimulation applied to bilateral anterior tibial muscles, where Zusanli (ST36) acupoints are located, once a day (30 min) for 3 successive days significantly enhanced splenic natural killer (NK) cell activity in BALB/c mice. The percentage of splenic NK cells, as measured by flow cytometry, was not affected in these mice. Interferon (IFN)-gamma level in splenic aqueous extract, prepared from the ST36 acupoint-stimulated mice, was significantly higher than that of the controls. In vivo treatment with neutralizing monoclonal antibody against mouse IFN-gamma completely abrogated the increase in splenic NK cell activity induced by ST36 acupoint stimulation. The same stimulation also significantly increased the concentration of splenic beta-endorphin, which coincided with the significant increase in splenic IFN-gamma production. Pre-administration of 10 mg/kg naloxone before initiation of EA stimulation every day reduced the enhancements of NK cell activity and IFN-gamma level. These observations strongly suggest that endogenous IFN-gamma mediates the up-regulation of NK cell activity by EA stimulation at the ST36 acupoints. Furthermore, endogenous beta-endorphin secreted by EA stimulation also plays an important role in the up-regulation of NK cell function, which may be realized through regulating IFN-gamma production.

Animals↗