Publications (29) View all
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Article: Analysis of membrane antigens on neutrophils from patients with sepsis.
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ABSTRACT: The aim of the present study was to assess changes of cell membrane antigens on neutrophils in septic patients. Expression levels of neutrophil membrane antigens were measured employing a FACS calibur flow cytometer with several fluorescence-labeled monoclonal antibodies. Expression levels of the CD14 antigen were higher in patients with sepsis than in healthy individuals. In particular, the expression levels of CD14 increased in patients complicated by septic shock. Expression levels of TLR-4 were higher in patients with sepsis or septic shock than in healthy individuals. Expression levels of CD11b and CD16 were lower in patients with sepsis or septic shock than in healthy individuals and were even lower in those complicated by septic shock. Expression levels of neutrophil membrane antigens in patients with sepsis markedly changed in the acute phase. However, these levels tended to return to those of healthy individuals in the convalescing phase. Analyses of the surface antigens on neutrophils strongly involved in biological defense or tissue injury are informative for understanding the pathology of sepsis and for conducting therapy targeting neutrophils in the future.Journal of Infection and Chemotherapy 03/2012; · 1.80 Impact Factor -
Article: Recurrent Helicobacter cinaedi Cellulitis and Bacteremia in a Patient with Systemic Lupus Erythematosus.
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ABSTRACT: A 31-year-old woman who had developed systemic lupus erythematosus at 17 years of age was admitted to the hospital for suspected cellulitis in the lower extremities. A blood culture performed upon admission to the hospital detected Helicobacter cinaedi (H. cinaedi), which was also isolated in blood and fecal cultures obtained on the 42nd hospital day. Bacterial translocation of H. cinaedi present in the intestines may have led to the development of recurrent bacteremia and cellulitis. In cases such as this, appropriate antibiotics therapy might be needed for more than one month. Moreover, H. cinaedi, a cause of emerging infections, requires a long period of time to grow; therefore it is important to extend the culture duration when the presence of this bacterium is suspected.Internal Medicine 01/2012; 51(22):3185-8. · 0.94 Impact Factor -
Article: Apoptotic signaling in endothelial cells with neutrophil activation.
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ABSTRACT: As is the case for tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), degranulated substances (DS) released from polymorphonuclear leukocytes (PMN) and H(2)O(2) cause endothelial cell apoptosis through the phosphorylation of members of the mitogen-activated protein kinase (MAPK) family. Stimulation of human umbilical vein endothelial cells (HUVEC) with IL-1β or TNF-α/cycloheximide (CHX) was found to enhance the phosphorylation of p38 and Jun-N-terminal kinase (JNK) in a time-dependent fashion, but did not affect the time-dependent phosphorylation of extracellular signal-regulated kinase. In addition, IL-1β and TNF-α/CHX induced the phosphorylation of activating transcription factor-2 (ATF-2), but not c-Jun. Moreover, the p38 in HUVEC was phosphorylated by DS released from PMN and also by H(2)O(2), but not by •O(2) (-) induced by myeloperoxidase (MPO) of PMN. On the other hand, caspase 8 in HUVEC was activated by DS, but not by H(2)O(2) and/or •O(2) (-). In addition, caspases 3 and 7 were cleaved by the treatment of DS and turned into active forms. DS was concentrated, analyzed by electrophoresis, and revealed to contain precursor and subunits of MPO (90, 60, and 14 kDa) and another peptide with a molecular weight of about 28 kDa. Because SB203580 that was an inhibitor of p38 MAPK did not repress phosphorylation of ATF-2 in HUVEC, it was suggested that JNK was more important than p38 in a series of signaling courses. These results suggest the possibility that not only TNF-α/CHX and IL-1β but also DS released from PMN and the cell-permeable reactive oxygen species H(2)O(2) induce blood vessel injury through endothelial apoptosis.Molecular and Cellular Biochemistry 12/2011; 363(1-2):269-80. · 2.06 Impact Factor -
Article: Suppression of phosphorylation of extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase in polymorphonuclear leukocytes by the proton pump inhibitor lansoprazole.
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ABSTRACT: Lansoprazole (LPZ) is a proton pump inhibitor that suppresses gastric secretion and exerts anti-inflammatory effects on immune cells. Recently, LPZ has been used for the treatment of peptic ulcer and gastritis, which can be caused by Helicobacter pylori, due to its potent acid-suppressive effects. We focused the aim to the anti-inflammatory effects on the over-activation of neutrophils, and investigated the effects of LPZ on the signal transduction of the mitogen-activated protein kinase (MAPK) family. LPZ slightly phosphorylated p38 MAPK of neutrophils at a concentration of 10 microg/ml , but did not phosphorylate extracellular-signal regulated kinase (ERK) 1/2. Pretreatment of neutrophils with (1-5 microg/ml ) LPZ strongly attenuated the phorbol-12-myristate-13-acetate-stimulated phosphorylation of ERK1/2, and LPZ slightly suppressed the lipopolysaccharide (LPS)- and N-formylmethionylleucylphenylalanine-stimulated phosphorylation of p38. ERK1/2 produces the mitochondrial anti-apoptotic proteins, and the signaling pathway from LPS and N-formylmethionylleucylphenylalanine to p38 is the main pathway for reactive oxygen species production. The mechanism of anti-inflammatory effect of LPZ on hyper-activated neutrophils is suggested to be the suppression of signal transduction of ERK1/2 and p38 MAPK.Journal of Infection and Chemotherapy 04/2010; 16(2):100-6. · 1.80 Impact Factor -
Article: Downregulation of immunomodulator gene expression in LPS-stimulated human polymorphonuclear leukocytes by the proton pump inhibitor lansoprazole.
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ABSTRACT: Lansoprazole (LPZ) has anti-inflammatory activity and repairs cells damaged by phagocytic cells. In the present study, we evaluated the effects of LPZ on gene expression, especially that of immunomodulator genes, in human polymorphonuclear leukocytes (PMNs) activated by lipopolysaccharide (LPS). Several concentrations of LPZ (final concentrations, 0-10 microg/ml) were added to the PMNs (1 x 10(6) cells/ml), which were stimulated with LPS (100 ng/ml) and incubated at 37 degrees C for 1 or 3 h. When LPS-stimulated PMNs were treated with LPZ at >or=5.0 microg/ml for 1 h, mRNA expression levels of CXCR1/2 and TNFalpha were suppressed in a dose-dependent manner. The gene expression level of CD14 was also downregulated by LPZ at >or=0.1 microg/ml, with expression suppressed to 50% by 10 microg/ml LPZ. However, LPZ at 0.01-5.0 microg/ml had no significant effect on the expression of TLR-4 or CD11b/CD18 mRNA. LPZ at 10 microg/ml downregulated the levels of these mRNAs to 80% and 50%, respectively. On the other hand, when the reaction period was extended to 3 h with the same conditions, all mRNA expression levels were downregulated by >or=0.01 microg/ml LPZ, in a dose-dependent manner. LPZ may suppress the biological functions of PMNs, such as chemotaxis and inflammatory chemokine production.Journal of Infection and Chemotherapy 12/2009; 15(6):374-9. · 1.80 Impact Factor
