PubMed Health⌕ Search

Biomedical subjects

Shuji Mori

Publications and source records attributed to Shuji Mori.

At least 19 recordsLinked to original sources
PubMed2006

Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice.

We examined whether treatment with amodiaquine, a potent inhibitor of histamine N-methyltransferase protects mice from Propionibacterium acnes (P. acnes)-primed and lipopolysaccharide (LPS)-induced hepatitis. The subcutaneous injection of amodiaquine (2 and 5 mg/kg) significantly increased the histamine levels in the liver in comparison to saline treated mice. Pretreatment with amodiaquine also improved the survival rate of the hepatitis mice, and this improvement was partially associated with the decrease in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Amodiaquine partially suppressed increases of tumor necrosis factor (TNF)-alpha in the serum and TNF-alpha mRNA expression in the liver, whereas the expression of interleukin (IL)-18, interferon (IFN)-gamma and IL-12 in the liver was not changed by amodiaquine treatment. In conclusion, the present findings suggested that the elevation of endogenous histamine by amodiaquine may thus play a protective role through the regulation of TNF-alpha production in endotoxin-induced hepatic injury mice.

Alanine Transaminase↗
PubMed2006

Clear distinction between preattentive and attentive process in schizophrenia by visual search performance.

Visual information-processing deficits were investigated in patients with schizophrenia using visual search tasks. Subjects comprised 20 patients with schizophrenia and 20 normal subjects. Visual search tasks were modified from those used previously to reveal more distinct differences between feature and conjunction search tasks. The presentation area of items in the present study was more than double the area used in our previous study [Mori, S., Tanaka, G., Ayaka, Y., Michitsuji, S., Niwa, H., Uemura, M., Ohta, Y., 1996. Preattentive and focal attentional processes in schizophrenia: a visual search study. Schizophrenia Research 22, 69-76], and items were distributed over the area randomly in each trial to produce a certain range of locational jitter for each item across trials that prevented a matrix-like presentation of items at fixed positions [Mori, S., Tanaka, G., Ayaka, Y., Michitsuji, S., Niwa, H., Uemura, M., Ohta, Y., 1996. Preattentive and focal attentional processes in schizophrenia: a visual search study. Schizophrenia Research 22, 69-76]. The target was a red square, and distractors were red circles in the feature search task and red circles and green squares in the conjunction search task. Slopes and intercepts of a linear function relating reaction times to set size were computed. In the feature search task, slopes for both groups were almost zero. In the conjunction search task, significant differences in slopes were seen between the two groups irrespective of target presence or absence. Moreover, the slopes were approximately twice as steep during target absence as during target presence. These results indicate more definitively than the results of our previous study [Mori, S., Tanaka, G., Ayaka, Y., Michitsuji, S., Niwa, H., Uemura, M., Ohta, Y., 1996. Preattentive and focal attentional processes in schizophrenia: a visual search study. Schizophrenia Research 22, 69-76] that patients with schizophrenia have deficits in focal attentional processing, although their preattentive processing functions at a normal level.

Adolescent↗
PubMed2006

The immunosuppressive effects of ciprofloxacin during human mixed lymphocyte reaction.

Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, is known to induce the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes, the production of interferon (IFN)-gamma and IL-12 and the proliferation of lymphocytes during the human mixed lymphocyte reaction (MLR). Ciprofloxacin (CIP), which is useful for the clinical treatment of infections due to its antibacterial properties after transplantation, was shown to suppress the IFN-gamma and IL-12 production, the lymphocyte proliferation and the ICAM-1, B7.1, B7.2 and CD40 expression on monocytes during MLR in the presence of IL-18. CIP also induced the production of prostaglandin (PG) E2. In order to determine whether the effects of CIP on the expression of the activation markers were due to CIP-dependent production of PGE2, we examined the effect of cyclooxygenase (COX)-2 and protein kinase A (PKA) inhibitors on the actions of CIP. Thereby, the inhibitors were found to abolish the actions of CIP. These results therefore suggest that CIP might exert its immune modulatory effects via the production of PGE2.

B7-1 Antigen↗
PubMed2006

The effect of ciprofloxacin on CD14 and toll-like receptor-4 expression on human monocytes.

CD14/toll-like receptor (TLR)-4 complex on monocytes/macrophages can bind lipopolysaccharide (LPS) and transduce the signals intracellularly. An antibacterial drug, ciprofloxacin (CIP), has been reported to modulate the inflammatory and immune responses. In the present study, we examined the effects of CIP on the LPS-induced activation of monocytes isolated from human peripheral blood mononuclear cells (PBMC). CIP suppressed the expression of CD14, TLR-4, intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, and CD40 and the production of tumor necrosis factor (TNF)-alpha induced by LPS in monocytes. CIP induced the production of prostaglandin (PG)E2 and increased intracellular cyclic adenosine monophosphate (cAMP) levels. Cyclooxygenase (COX)-2 inhibitors, NS398 and indomethacin, reversed the effects of CIP on TNF-alpha production and reduced the levels of different surface antigens, whereas a protein kinase A (PKA) inhibitor, H89, did not. Therefore, CIP might regulate the TNF-alpha production induced by LPS by inhibiting the expression of LPS receptor complex, which seems to be mediated by COX-2 but not the cAMP/PKA pathway.

Antigens, CD↗
PubMed2005

Beta2-adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12 production in monocytes.

We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on monocyte-derived cytokines, interleukin (IL)-18 and IL-12 production in lipopolysaccharide (LPS)-stimulated monocytes derived from human peripheral blood mononuclear cells (PBMCs), as in vitro model of sepsis. The study found that beta2-AR agonists inhibited IL-18 and IL-12 production in monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar inhibitory pattern of IL-18 and IL-12 production. IL-12 production induced by LPS was inhibited by anti-IL-18 Ab, but IL-18 production by LPS was not inhibited by anti-IL-12 Ab, showing that LPS induced IL-18 production without IL-12 production. Therefore, the stimulation of beta2-AR might be beneficial in the treatment of sepsis through inhibiting LPS-elicited IL-18.

Adrenergic beta-2 Receptor Agonists↗
PubMed2005

Mast cell tryptase stimulates DLD-1 carcinoma through prostaglandin- and MAP kinase-dependent manners.

We found that striptease-positive mast cells were abundant in the invasive front of human colon adenocarcinoma by examining 30 cases. Because tryptase has been suggested to be the agonist proteinase for protease-activated receptor-2 (PAR-2), we investigated the effects of stimulation of PAR-2 by tryptase on the cell signaling and proliferation of DLD-1, a human colon carcinoma cell line. PAR-2 stimulation by tryptase induced the increase in [Ca(2+)](i), which was desensitized by the prior application of PAR-2 activating peptide (AP). The proliferative responses of DLD-1 to tryptase and PAR-2 AP were associated with the phosphorylation of MEK and MAP kinase. Inhibition of MEK by PD98059 completely inhibited the proliferation-enhancing effects of tryptase and PAR-2 AP as well as phosphorylation of MAP kinase. Moreover, tryptase and PAR-2 AP stimulated the production of prostaglandin E2 and the inhibition of prostaglandin synthesis by indomethacin or NS398 resulted in the complete inhibition of the proliferative responses to tryptase and PAR-2 AP. Furthermore, the tryptase-stimulated proliferation of DLD-1 was concentration-dependently inhibited by nafamostat mesilate, a specific inhibitor of tryptase. These results as a whole indicated that tryptase has proliferative effects on DLD-1 through cyclooxygenase- and MAP kinase-dependent manners acting on PAR-2 by its proteolytic activity.

Benzamidines↗
PubMed2005

Nafamostat mesilate induces production of interleukin-12 and -18 in human peripheral blood mononuclear cells.

Little has been reported on the drugs inducing production of monocyte-derived cytokines like interleukin (IL)-18 and IL-12. We found that nafamostat mesilate elicits IL-12, IL-18, tumor necrosis factor-alpha and interferon-gamma production, and the expression of intercellular adhesion molecules-1, B7.1, B7.2, CD40, and CD40 ligand in human peripheral blood mononuclear cells. The cytokine production and adhesion molecule expression were abolished by anti-IL-12 and IL-18 antibodies. Therefore, IL-18 and IL-12 may play roles in the significant and immediate effects of nafamostat mesilate.

Benzamidines↗
PubMed2005

Prostaglandins E1 and E2 inhibit lipopolysaccharide-induced interleukin-18 production in monocytes.

The purpose of this present study was to explore the therapeutic potential of prostaglandins E1 and E2 on the systemic inflammatory response evoked by endotoxin. Since interleukin-18, a monocyte-derived cytokine, is increased during sepsis, decreasing the production of interleukin-18 is important in treating this condition. Prostaglandin E1 and E2 inhibited interleukin-18 production in human monocytes treated with lipopolysaccharide and prostanoid IP-, EP2- and EP4-receptor agonists mimicked the effects of prostaglandins E1 and E2. Therefore, prostanoid IP, EP2- and EP4-receptors might be involved in the decrease in interleukin-18 production during sepsis.

Alprostadil↗
PubMed2005

Differential effect of prostaglandins E1 and E2 on lipopolysaccharide-induced adhesion molecule expression on human monocytes.

The effect of prostaglandins E1 and E2 on the 1 ng/ml lipopolysaccharide-induced expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes was examined. Prostaglandin E1 suppressed B7.1 and CD40 expression, but prostaglandin E2 did not effect on any type of adhesion molecule expression. Both prostaglandins inhibited tumor necrosis factor (TNF)-alpha production and T-cell proliferation of lipopolysaccharide-treated human peripheral blood mononuclear cells (PBMC). Among prostaglandin E1 receptors (IP/EP1/EP2/EP3/EP4) agonists, ONO-1301, a prostanoid IP-receptor agonist, prevented B7.1 and CD40 expression. ONO-AE1-259-01 a prostanoid EP2-receptor agonist, ONO-AE1-329, a prostanoid EP4-receptor agonist, and ONO-1301 inhibited TNF-alpha production and T-cell proliferation. Moreover, anti-B7.1 and anti-CD40 Abs prevented lipopolysaccharide-induced TNF-alpha production and T-cell proliferation. Therefore, the effect of prostaglandin E1 on TNF-alpha production and T-cell proliferation might depend on the inhibition of B7.1 and CD40 expression, but that of prostaglandin E2 might be independent of adhesion molecules expression. In conclusion, the mechanism responsible for the effect of prostaglandin E1 on lipopolysaccharide-induced responses is distinct from that of prostaglandin E2.

Alprostadil↗
PubMed2005

Effect of antibodies against intercellular adhesion molecule-1, B7, and CD40 on interleukin-18-treated human mixed lymphocyte reaction.

The interleukin (IL)-18 level in plasma is elevated during the acute rejection after organ transplantation. IL-18 elicits adhesion molecule expression as well as interferon-gamma/IL-12 production and T-cell proliferation in the human mixed lymphocyte reaction, an in vitro model of acute rejection. We examined whether antibodies (Abs) against intercellular adhesion molecule (ICAM)-1, B7, CD40, and CD40, ligand (CD40L) affect the cytokine production and T-cell proliferation. Anti-ICAM-1 and B7 Abs suppressed the cytokine production, while all Abs inhibited T-cell proliferation. ICAM-1 and B7 as well as CD40 may play different roles in the acute rejection.

Antibodies↗
PubMed2005

Physiology and pathophysiology of proteinase-activated receptors (PARs): PAR-2-mediated proliferation of colon cancer cell.

Proteinase-activated receptor-2 (PAR-2) has been demonstrated to be highly expressed in the gastrointestinal tract. In the present minireview, we summarize the effects of PAR-1 and PAR-2 stimulation using their activating peptides and agonist proteinases on the calcium signaling and the cell proliferation in DLD-1 cell, a human colon cancer cell line. PAR-2 but not PAR-1 stimulation induced the enhancement of cell proliferation, whereas both PAR-1 and PAR-2 stimulation induced the transient increase in [Ca(2+)](i). PAR-2 stimulation induced the phosphorylation of MEK1/2 and ERK1/2, but PAR-1 stimulation did not. The inhibition of MEK1/2 by PD98059 completely abolished the proliferative response to PAR-2 stimulation. Thus, MEK-ERK activation plays major role in the PAR-2-mediated proliferative response. The coupling of PARs to calcium signaling and MEK-ERK activation may be independent, and varied dependent on cell types.

Animals↗
PubMed2005

Prostaglandin E1-initiated immune regulation during human mixed lymphocyte reaction.

Prostaglandin E1 (PGE1) has therapeutic value for transplantations due to its microvascular activity. Interleukin (IL)-18, which is elevated in plasma during the acute rejection after organ transplantation, elicits the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on monocytes as well as the production of interferon (IFN)-gamma and IL-12 and proliferation of T-cells during the human mixed lymphocyte reaction (MLR) in an in vitro model of acute rejection. In contrast, PGE1 inhibits all the adhesion molecule expression, cytokine production and T-cell proliferation in the presence of IL-18. The effects of PGE1 depend on stimulation of the IP/EP2/EP4-receptor, and thus, PGE1 might have therapeutic potential for treating acute rejection due to its immune regulatory effect.

Alprostadil↗
PubMed2005

Simvastatin induces interleukin-18 production in human peripheral blood mononuclear cells.

The effects of statins on immune response depend on the inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and leukocyte function-associated antigen (LFA)-1, which is a ligand of intercellular adhesion molecule (ICAM)-1. Simvastatin, an HMG-CoA reductase inhibitor with mild inhibition of LFA-1, induced the production of interleukin (IL)-18, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in human peripheral blood mononuclear cells (PBMC). The IL-18 production is located upstream of the cytokine cascade activated by simvastatin. Moreover, simvastatin concentration-dependently inhibited the expression of ICAM-1 and induced the expression of CD40 on monocytes. In the presence of IL-18, simvastatin suppressed the expression of ICAM-1 and CD40 as well as the production of IL-12, TNF-alpha and IFN-gamma in PBMC, contributing to the anti-inflammatory effect of simvastatin. The effects of simvastatin were abolished by the addition of the product of the HMG-CoA reductase, mevalonate, indicating the involvement of HMG-CoA reductase in the action of simvastatin.

Adult↗
PubMed2005

Effect of ciprofloxacin-induced prostaglandin E2 on interleukin-18-treated monocytes.

Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E(2) in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E(2) and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E(2) and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.

Anti-Bacterial Agents↗
PubMed2004

Differential effect of LFA703, pravastatin, and fluvastatin on production of IL-18 and expression of ICAM-1 and CD40 in human monocytes.

A novel, proinflammatory cytokine, interleukin (IL)-18 production was detected in the medium of human monocytes treated with 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, pravastatin, and fluvastatin (0.1 and 1 muM) but not with the statin-derived lymphocyte function-associated antigen-1 (LFA-1) inhibitor LFA703, which did not inhibit HMG-CoA reductase. Pravastatin and fluvastatin also induced the production of IL-18, tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in human peripheral blood mononuclear cells (PBMC) in contrast to LFA703. IL-18 production by PBMC is located upstream of the cytokine cascade activated by these statins. The IL-18-induced cytokine production was demonstrated to be dependent on adhesion molecule expression on monocytes. In the absence and presence of lower concentrations (0.1 and 1 ng/ml) of IL-18, pravastatin and fluvastatin inhibited the expression of intercellular adhesion molecule (ICAM)-1 and induced the expression of CD40, whereas LFA703 had no effect. In the presence of higher concentrations (5, 10, and 100 ng/ml) of IL-18, pravastatin, fluvastatin, and LFA703 similarly inhibited the expression of ICAM-1 and CD40 as well as the production of IL-12, TNF-alpha, and IFN-gamma in PBMC. The effects of pravastatin and fluvastatin but not LFA703 were abolished by the addition of mevalonate, indicating the involvement of HMG-CoA reductase in the action of pravastatin and fluvastatin. Thus, the effects of LFA703 were distinct from those of pravastatin and fluvastatin in the presence of lower concentrations of IL-18. It was concluded that LFA703 has the inhibitory effect on an IL-18-initiated immune response without any activation on monocytes.

Antibodies, Monoclonal↗
PubMed2004

E-prostanoid (EP)2/EP4 receptor-dependent maturation of human monocyte-derived dendritic cells and induction of helper T2 polarization.

Prostaglandin (PG) E(2) induces dendritic cell maturation in cooperation with proinflammatory cytokines [such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta]. To clarify the involvement of E-prostanoid (EP) receptors in the effect of prostaglandin E(2) on human monocyte-derived dendritic cell (MoDC) maturation, we examined the effect of four types of EP receptor-selective agonists on MoDC maturation. PGE(2) as well as 11,15-O-dimethyl prostaglandin (E(2)ONO-AE1-259-01) (EP2 receptor agonist) and ONO-AE1-329 (EP4 receptor agonist) concentration dependently enhanced the expression of CD80, CD86, CD83, and HLA-DR on MoDCs during maturation, especially in the presence of TNF-alpha, whereas 17S-2,5-ethano-6-oxo-17,20-dimethyl prostaglandin E(1) (EP1 receptor agonist) and 16S-9-deoxy-9beta-chloro-15-deoxy-16-hyfroxy-17,17-trimethylene-19,20-didehydro prostaglandin F(2) (EP3 receptor agonist) showed no effect. The maximal effect of ONO-AE1-259-01 was higher than that of ONO-AE1-329; however, the stimulation with ONO-AE1-259-01 was less effective than that with PGE(2). Simultaneous stimulation with both EP receptor agonists produced additive effects and 11-deoxy-PGE(1) (EP2/EP4 receptor mixed agonist) mimicked the effects of PGE(2). Dibutyryl cAMP mimicked the effects of PGE(2), indicating the mediation of PGE(2) action by cAMP. Matured MoDCs induced by PGE(2) or EP2 and/or EP4 receptor agonists showed a decrease in lipopolysaccharide (LPS)-stimulated IL-12p70, IL-6, and IL-10 production. The coculture of naive T cells with matured MoDCs induced under different conditions showed that EP2/EP4-stimulated MoDCs preferentially induced alloresponsive helper T (Th)2 cells. Together, it was concluded that the cooperative stimulation of EP2 and EP4 receptor subtypes by PGE(2) promoted MoDC maturation and inhibited LPS-induced cytokine production in MoDCs. The matured MoDCs under such conditions preferably induced Th2 polarization, indicating the importance of EP2 and EP4 receptors in the determination of Th1/Th2 development of naive T cells.

Antigens, CD↗
PubMed2004

Effect of beta2-adrenergic receptor agonists on intercellular adhesion molecule (ICAM)-1, B7, and CD40 expression in mixed lymphocyte reaction.

BACKGROUND: The plasma interleukin (IL)-18 level is elevated in acute rejection after organ transplantation. Although beta2-adrenergic receptor (AR) agonists suppress the rejection of organ and tissue transplants, little is known about their action mechanisms. We examined the effects of endogenous catecholamines and beta2-AR agonists on the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) in human mixed lymphocyte reaction (MLR) and in an in vitro model of acute rejection in the presence or absence of IL-18. METHODS: ICAM-1, B7.1 B7.2, CD40, and CD40L expression on monocytes was measured by flow cytometry, and the production of interferon (IFN)-gamma and IL-12 was determined by enzyme-linked immunosorbent assay. Lymphocytes proliferation in MLR was measured by [3H]-thymidine uptake. The relevant AR subtypes were characterized using subtype-selective agonists and antagonists. RESULTS: beta2-AR agonists inhibited the expression of ICAM-1 and CD40 during MLR in the absence of IL-18. Among IL-18-induced expression of ICAM-1, B7.1, B7.2, CD40, and CD40L, beta2-AR agonists inhibited ICAM-1 and CD40 expression. beta2-AR agonists prevented the production of IFN-gamma and IL-12 in the presence of IL-18 but had no effect in the absence of IL-18. beta2-AR agonists inhibited lymphocyte proliferation in IL-18-treated MLR. CONCLUSIONS: We found that beta2-AR agonists strongly inhibited the expression of ICAM-1 and CD40, irrespective of the presence or absence of IL-18, which is different from that of histamine and prostaglandin E2.

Adrenergic beta-Agonists↗