A5103047709- Inflammatory Bowel Disease
- Microbial Natural Products and Biosynthesis
- Microscopic Colitis
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Helicobacter pylori-related gastroenterology studies
- Bacterial Genetics and Biotechnology
- Eosinophilic Esophagitis
- Genomics and Phylogenetic Studies
- T-cell and B-cell Immunology
- Fungal Biology and Applications
- Synthetic Organic Chemistry Methods
- Bacteriophages and microbial interactions
- IL-33, ST2, and ILC Pathways
- Fungal and yeast genetics research
- Mycobacterium research and diagnosis
- Gut microbiota and health
- RNA modifications and cancer
- Gastric Cancer Management and Outcomes
- Marine Sponges and Natural Products
- Gastrointestinal Bleeding Diagnosis and Treatment
- Pregnancy and Medication Impact
- Immune cells in cancer
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
National Agriculture and Food Research Organization
2019-2024
Kyorin University
2015-2023
Food Research Institute
2004-2019
Keio University
2006-2018
Food Research Institute
1998-2018
Keio University Hospital
2005-2013
Kagoshima University
2013
Musashino University
2008-2011
University of Salento
2008
NTT (Japan)
2006
Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal lack the expression innate-immune receptor CD14 and do not produce proinflammatory cytokines this study, we identified what believe to be unique macrophage subset human intestine. This expressed both (CD14, CD33, CD68) DC markers (CD205, CD209) produced larger amounts cytokines, such as IL-23, TNF-α, IL-6, than typical resident (CD14–CD33+ macrophages). patients...
Streptomycin has been an important drug for the treatment of tuberculosis since its discovery in 1944. But numerous strains Mycobacterium tuberculosis, bacterial pathogen that causes are now streptomycin resistant. Although such resistance is often mediated by mutations within rrs, a 16S rRNA gene or rpsL, which encodes ribosomal protein S12, these found limited proportion clinically isolated streptomycin-resistant M. strains. Here we have succeeded identifying mutation confers low-level to...
A strain of Streptomyces lividans, TK24, was found to produce a pigmented antibiotic, actinorhodin, although S. lividans normally does not this antibiotic. Genetic analyses revealed that streptomycin-resistant mutation str-6 in TK24 is responsible for induction antibiotic synthesis. DNA sequencing showed point the rpsL gene encoding ribosomal protein S12, changing Lys-88 Glu. Gene replacement experiments with Lys88-->Glu str allele demonstrated unambiguously alone activation actinorhodin...
We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of mucosal lymphocytes expressing functional receptor. To clarify the mechanism by which locally produced regulates lymphocytes, we investigated transgenic mice. Here report mice murine cDNA driver SRα promoter developed chronic colitis in concert with expression SRα/IL-7 transgene colonic mucosa. but not littermate at 4–12 wk age,...
Disorders in enteric bacteria recognition by intestinal macrophages (Mphi) are strongly correlated with the pathogenesis of chronic colitis; however precise mechanisms remain unclear. The aim current study was to elucidate roles Mphi inflammation using an IL-10-deficient (IL-10-/-) mouse colitis model. GM-CSF-induced bone marrow-derived (GM-Mphi) and M-CSF-induced (M-Mphi) were generated from marrow CD11b+ cells. M-Mphi IL-10-/- mice produced abnormally large amounts IL-12 IL-23 upon...
OBJECTIVE The clinical significance of cytomegalovirus (CMV) reactivation complicating ulcerative colitis (UC) patients has been uncertain. It therefore remained undetermined whether or not CMV should be treated in UC under immunosuppression. aim the study was to clarify natural history patients. METHODS Sixty-nine with moderate severe activity were enrolled study. All prednisolone, and/or immunosuppressants such as cyclosporine A. We sequentially monitored every 2 wk up until 8 using...
Signaling lymphocyte activation molecule (SLAM), a glycoprotein expressed on activated lymphocytes and antigen-presenting cells, has been shown to be coregulator of antigen-driven T cell responses is one the two receptors for measles virus. Here we show that receptor–induced interleukin (IL)-4 secretion by SLAM−/− CD4+ cells down-regulated, whereas interferon γ production only slightly up-regulated. Although SLAM controls IL-12, tumor necrosis factor, nitric oxide in response...
Background Inflammatory bowel disease (IBD) is a chronic intestinal disorder that associated with limited number of clinical biomarkers. In order to facilitate the diagnosis IBD and assess its activity, we investigated potential novel multivariate indexes using statistical modeling plasma amino acid concentrations (aminogram). Methodology Principal Findings We measured fasting aminograms in 387 patients (Crohn's (CD), n = 165; ulcerative colitis (UC), 222) 210 healthy controls. Based on...
Lamina propria macrophages (LPMs) spontaneously produce large amounts of anti-inflammatory IL-10 and play a central role in regulation immune responses against commensal bacteria. MCP-1 is chemokine that plays an important recruitment monocytes to inflamed tissues. We demonstrated that, addition IL-10, LPMs produced MCP-1, even steady state. deficiency caused impaired production by led exacerbation dextran sulfate sodium-induced acute colitis. As explanation this LPMs, we found could be...
Virginiae butanolides (VBs) A-E are butyrolactone autoregulators that control virginiamycin production in Streptomyces virginiae. We have previously reported the purification and molecular cloning of VbrA, a putative VB binding protein (Okamoto, S., Nihira, T., Kataoka, H., Suzuki, A., Yamada, Y.(1992) J. Biol. Chem. 267, 1093-1098). However, VbrA [Abstract] overexpressed Escherichia coli did not show any detectable activity nor immunoprecipitation native from cell-free extract S. virginiae...
ABSTRACT We have found a novel phospholipid antibiotic (named bacilysocin) which accumulates within (or associates with) the cells of Bacillus subtilis 168 and determined structure by nuclear magnetic resonance mass spectrometry analyses. The bacilysocin elucidated was 1-(12-methyltetradecanoyl)-3-phosphoglyceroglycerol. Bacilysocin demonstrated antimicrobial activity, especially against certain fungi. Production commenced immediately after growth ceased before formation heat-resistant...
Abstract Background Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily and contributes to pathogenesis Crohn's disease (CD) by stimulating T-helper (Th) 1 cells. In addition Th1, recent studies have focused on role Th17 cells in CD. Here we tried clarify TL1A Th1 immunity Methods expression was assessed quantitative reverse-transcription polymerase chain reaction (RT-PCR) lamina propria (LP) macrophages (LP-MΦs) from normal controls (NC) patients with CD or...
Despite their importance in the chemical industry, significance of rare earths biology has been largely overlooked. Here, it is reported that earth, scandium (Sc), causes antibiotic overproduction by 2-25-fold when added at a low concentration (10-100 microM) to cultures Streptomyces coelicolor A3(2) (actinorhodin producer), antibioticus (actinomycin and griseus (streptomycin producer). Not just for enhancement production, was also effective activating dormant ability produce actinorhodin...
Intestinal APCs are considered critical in maintaining the balance between response against harmful pathogens and induction of tolerance to commensal bacteria food Ags. Recently, several studies indicated presence gut-specific APC subsets, which possess both macrophage dendritic cell (DC) markers. These unique subsets play important roles gut immunity, especially for immune regulation bacteria. Herein, we examined a subset, coexpressed (Mphi) marker CD14 DC CD209 human intestinal lamina...
ABSTRACT We found that a 46-kDa protein is highly expressed in an actinorhodin-overproducing Streptomyces coelicolor A3(2) mutant (KO-179), which exhibited low-level resistance to streptomycin. The was identified as S -adenosylmethionine (SAM) synthetase, product of the metK gene. Enzyme assay revealed SAM synthetase activity strain KO-179 5- 10-fold higher than wild-type cells. elevation be associated with increase level intracellular SAM. RNase protection gene transcribed from two distinct...
ABSTRACT Physiological differentiation (including antibiotic production) in microorganisms usually starts when cells encounter adverse environmental conditions and is frequently accompanied by an increase the accumulation of intracellular ppGpp. We have found that acquisition certain streptomycin-resistant ( str ) mutations enables to overproduce antibiotics, demonstrating productivity 5- 50-fold greater than wild-type strains. The frequency such antibiotic-overproducing strains among...
The Streptomyces coelicolor obg gene, which encodes a putative GTP‐binding protein of the Obg/Gtp1 family, was characterized. gene essential for viability. Introduction multiple copies into wild‐type S. suppressed aerial mycelium formation. A single amino acid substitution at any six positions introduced GTP binding site Obg, and mutated proteins were expressed in cells. Obg P168 → V exerted more accentuated suppressive effect on formation than did protein. In contrast, G171 accelerated...
Certain str mutations that confer high- or low-level streptomycin resistance result in the overproduction of antibiotics by Streptomyces spp. The high-level occur within rpsL, which encodes ribosomal protein S12, while those cause are not as well known. We have used comparative genome sequencing to determine is caused rsmG, an S-adenosylmethionine (SAM)-dependent 16S rRNA methyltransferase containing a SAM binding motif. Deletion rsmG from wild-type coelicolor resulted acquisition and...
Ulcerative colitis (UC) involves intestinal mucosal damage induced by reactive oxygen species (ROS), in particular, superoxide anion. Superoxide dismutase (SOD) catalyzes dismutation of anion to hydrogen peroxide, which is subsequently detoxified catalase. Lecithinized SOD (PC-SOD) a new modified form that has overcome previous clinical limitations SOD. In this study, we examined the action PC-SOD using an animal model UC, dextran sulfate sodium (DSS)-induced colitis. DSS-induced was...
ABSTRACT Certain streptomycin resistance mutations (i.e., rpsL and rsmG ) result in the overproduction of antibiotics various actinomycetes. Moreover, double-mutant strains show a further increase antibiotic production. but not marked enhancement oligomycin production Streptomyces avermitilis erythromycin Saccharopolyspora erythraea , accompanied by increased transcription key developmental regulator gene, bldD latter organism.
CX3CL1/Fractalkine (FKN) has been reported to play important roles in various inflammatory diseases. We examined the role of FKN and its receptor CX3CR1 T-cell migration bowel diseases (IBDs), ulcerative colitis (UC) Crohn's disease (CD). expression on peripheral CD4+ cells from normal controls (NL n = 24) IBD patients (UC 28, CD 26) was using flow cytometry. CX3CR1+CD4+ T were further characterized for surface antigens, cytokine production, cytotoxic granule release by cytometry ELISA. 53...