Non-cell-autonomous suppression of tumor growth by RECK in immunocompetent mice.

RECK is a candidate tumor suppressor gene isolated as a gene that induces flat reversion in a cell line transformed by the KRAS oncogene. Since RECK knockout mice die in utero, they are not suitable for studying the effects of RECK on tumor formation. In this study, we found an increased incidence of spontaneous pulmonary adenomas in mice with reduced RECK expression (RECK-Hypo mice).

Sufficient water intake maintains the gut microbiota and immune homeostasis and promotes pathogen elimination.

Water is the most abundant substance in the human body and plays a pivotal role in various bodily functions. While underhydration is associated with the incidence of certain diseases, the specific role of water in gut function remains largely unexplored. Here, we show that water restriction disrupts gut homeostasis, which is accompanied by a bloom of gut microbes and decreased numbers of immune cells, especially T17 cells, within the colon.

Fasting impairs type 2 helper T cell infiltration in the lung of an eosinophilic asthma mouse model.

Eosinophilic asthma is a form of bronchial asthma that is caused by the pulmonary infiltration of eosinophils and accounts for approximately half of the patients with severe asthma. Several cell types of the immune system in synergy with the epithelial cells of the lung provoke an inflammatory response in patients with asthma. Recently, the effect of fasting on immune cells and inflammation has attracted considerable attention.

Complete Genome Sequence of Bifidobacterium longum Strain Jih1, Isolated from Human Feces.

We report the complete genome sequence of strain Jih1, isolated from human feces. The assembled genome comprised one circular chromosome of 2.37 Mb.

Synthetic Biomarker Design by Using Analyte-Responsive Acetaminophen.

The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy that uses analyte-responsive acetaminophen (APAP) to expand the catalogue of analytes available for synthetic biomarker development. As proof-of-concept, we designed hydrogen peroxide (H O )-responsive APAP (HR-APAP) and succeeded in H O detection with cellular and animal experiments.

Modification of Gene Expression, Proliferation, and Function of OP9 Stroma Cells by Bcr-Abl-Expressing Leukemia Cells.

Expression of the Bcr-Abl fusion gene in hematopoietic progenitor cells (HPCs) results in the development of chronic myelogenous leukemia (CML), for which hematopoietic microenvironment plays an important role. We investigated the specific effects of an HPC line transduced with Bcr-Abl, KOBA, on BM-derived OP9 stroma cells. DNA microarray analysis revealed that OP9 cells co-cultured with KOBA cells (OP9/L) show diverse changes in the gene expression.

A CD153+CD4+ T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production.

Immune aging results in diminished adaptive immunity and increased risk for autoimmunity. We previously reported a unique PD-1(+) CD44(high)CD4(+) T cell population that increases with age in normal mice. In this study, we indicate that the age-dependent PD-1(+) CD44(high)CD4(+) T cells develop as unique T follicular (TF) cells in a B cell-dependent manner and consist of two subpopulations, as follows: CD153(+) cells preferentially secreting abundant osteopontin on TCR stimulation and CD153(-) cells that are apparently TCR anergic.

Crucial role of the Rap G protein signal in Notch activation and leukemogenicity of T-cell acute lymphoblastic leukemia.

The Rap G protein signal regulates Notch activation in early thymic progenitor cells, and deregulated Rap activation (Rap(high)) results in the development of Notch-dependent T-cell acute lymphoblastic leukemia (T-ALL). We demonstrate that the Rap signal is required for the proliferation and leukemogenesis of established Notch-dependent T-ALL cell lines. Attenuation of the Rap signal by the expression of a dominant-negative Rap1A17 or Rap1GAP, Sipa1, in a T-ALL cell line resulted in the reduced Notch processing at site 2 due to impaired maturation of Adam10.

Intracellular delivery of lipopolysaccharide induces effective Th1-immune responses independent of IL-12.

Lipopolysaccharide (LPS) is responsible for many of the inflammatory responses and pathogenic effects of Gram-negative bacteria, however, it also induces protective immune responses. LPS induces the production of inflammatory cytokines such as TNF-α, IL-6, and IL-12 from dendritic cells (DCs) and macrophages. It is thought that IL-12 is required for one of the protective immune responses induced by LPS, the T helper 1 (Th1)-immune response, which include the production of IFN-γ from Th1cells and IgG2c class switching.

Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14.

Lipopolysaccharide (LPS) is recognized by CD14 with Toll-like receptor 4 (TLR4), and initiates 2 major pathways of TLR4 signaling, the MyD88-dependent and TRIF-dependent signaling pathways. The MyD88-dependent pathway induces inflammatory responses such as the production of TNF-α, IL-6, and IL-12 via the activation of NFκB and MAPK. The TRIF-dependent pathway induces the production of type-I IFN, and RANTES via the activation of IRF-3 and NFκB, and is also important for the induction of adaptive immune responses.

Effects of CB-VEGF-A injection in rat flap models for improved survival.

Background: Various carriers have been tested as drug delivery systems in an attempt to sustain the action of growth factors. Gene therapy has also been adopted to achieve lasting effects but without satisfactory results. Because the authors believe that the angiogenic effect of vascular endothelial growth factor (VEGF) can be enhanced by anchoring the fusion protein composed of the Clostridium-derived collagen-binding domain and recombinant VEGF-A164 (CB-VEGF-A) in the tissue, they examined the changes in blood flow of random pattern flaps following treatment of the dorsal region of the rat with the fusion proteins before skin flap elevation.

Potentiation of murine innate immunity by alpha-galacturonosyl-type glycosphingolipids isolated from Sphingomonas yanoikuyae and S. terrae.

Glycosphingolipids (GSLs) are components of the outer membrane of Sphingomonas species, commonly classified into two types, alpha-glucuronosyl ceramide (alpha-GlcACer) and alpha-galacturonosyl ceramide (alpha-GalACer), respectively. GSL-7 from S. yanoikuyae and GSL-13 from S.

Liposomal glycosphingolipids activate natural killer T cell-mediated immune responses through the endosomal pathway.

Natural killer T (NKT) cells recognize lipid antigens, such as glycosphingolipids (GSLs), via CD1d and contribute to host defense against various pathogens. Here, we demonstrate that GSLs isolated from Sphingomonas bacteria and inserted into liposomes (GSL-liposomes) enhance the activation of NKT cells and dendritic cells (DCs). GSL-liposomes remarkably enhanced the production of IFN-gamma from splenocytes in vitro and this enhancement depended on the content of the pH-sensitive lipid dioleoyl-phosphoethanolamine (DOPE) in the liposomes.

Suppression of skin lesions by transdermal application of CpG-oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis.

Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by an elevation of the total IgE level in plasma, the infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 cells. NC/Nga mice kept in conventional conditions are known to develop skin lesions resembling human AD. We examined in this study the alterations of immune response in NC/Nga mice kept in conventional conditions, following transdermal application of CpG-oligodeoxynucleotides (ODN), which plays a critical role in immunity via the augmentation of Th1-type and suppression of Th2-type responses.

Cyclooxygenase-2 inhibition promotes enhancement of antitumor responses by transcutaneous vaccination with cytosine-phosphate-guanosine-oligodeoxynucleotides and model tumor antigen.

One of the principal goals in tumor immune prophylaxis and tumor therapy is the induction of antitumor responses by generating sufficient numbers of tumor antigen-specific helper T (Th)1 cells and cytotoxic T lymphocytes (CTLs). We have demonstrated that the administration of cytosine-phosphate-guanosine-oligodeoxynucleotide (CpG-ODN) through tape-stripped skin induced a Th1-type immune response and suggested that the skin is a potential site for vaccination. CpG-ODN induces the expression of cyclooxygenase (COX)-2, and its product prostaglandin (PG) E2 underlies an immunosuppressive network, therefore it is a simple strategy to use a COX-2 inhibitor for tumor vaccination with CpG-ODN.

Toll-like receptor-9 expression induced by tape-stripping triggers on effective immune response with CpG-oligodeoxynucleotides.

Recently, there has been a lot of interest in the potential of non-invasive routes, such as via the skin, for vaccine delivery. CpG-oligodeoxynucleotides (ODN) are an effective adjuvant for the induction of cellular and humoral immunities when administered with an antigen. We demonstrated here that tape-stripping induces the expression of toll-like receptor (TLR)-9 in the skin, and enhances the Th1-type immune response triggered by CpG-ODN administered through the tape-stripped skin.

Changes in immune responses to mite antigen sensitized through barrier-disrupted skin with CpG-oligodeoxynucleotide in mice.

CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to mite antigen sensitized through barrier-disrupted skin of human atopic dermatitis (AD) model mouse. Although sensitization with mite antigen induced Th2-dominant immune response, co-administration of CpG-ODN elicited Th1-predominant immune response.

Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice.

CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to tape-stripped mouse skin by evaluating the production of cytokines and Ig isotypes. Confocal laser scanning microscopy revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin.

Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in NC/Nga mice.

Purpose: CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and the suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to a tape-stripped skin of NC/Nga mouse, a human atopic dermatitis (AD) model, by evaluating the production of cytokines and immunoglobulin isotypes.

Methods: Model antigen, ovalbumin (OVA), and CpG-ODN were applied on to the shaved skin.