Features of T-cell subset composition in a D-galactose-induced senescence mouse model.

Long-term administration of D-galactose induces oxidative stress and accelerates normal age-related changes. Hence, the D-galactose-treated rodent model has been widely used for aging research. In this study, we examined the immunological characteristics, especially CD4 T-cell subset composition, of D-galactose-induced aging model mice to evaluate the model's utility in immunosenescence studies.

Effect of the 11/19-B1 Strain on Atopic Dermatitis in a Clinical Test and Mouse Model.

Some lactic acid bacteria (LAB) are known to improve atopic dermatitis (AD) through the regulation and stimulation of the host immune system. In this study, we found that ingestion of yogurt containing 11/19-B1 strain ( 11/19-B1) daily for 8 weeks significantly improved the severity scoring of atopic dermatitis (SCORAD) system score from 38.8 ± 14.

Cutting Edge: A Critical Role of Lesional T Follicular Helper Cells in the Pathogenesis of IgG4-Related Disease.

IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD.

Loss of sorting nexin 5 stabilizes internalized growth factor receptors to promote thyroid cancer progression.

Thyroid carcinoma is the most common endocrine malignancy and its prevalence has recently been increasing worldwide. We previously reported that the level of sorting nexin 5 (Snx5), an endosomal translocator, is preferentially decreased during the progression of well-differentiated thyroid carcinoma into poorly differentiated carcinoma. To address the functional role of Snx5 in the development and progression of thyroid carcinoma, we established Snx5-deficient (Snx5 ) mice.

High frequency of Bob1 T follicular helper cells in florid reactive follicular hyperplasia.

Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH.

Keratinocytes in atopic dermatitis express abundant ΔNp73 regulating thymic stromal lymphopoietin production via NF-κB.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that often cannot be completely controlled by modern medicine. Since multiple factors are intricately involved in the pathogenesis of AD, wide-ranging research is required for further advancement of AD treatment. Epidermal keratinocytes are the forefront to the external environment and play a pivotal role in the initiation of immune reaction against exogenous invasion.

Lipid mediators foster the differentiation of T follicular helper cells.

Lipid mediators such as leukotrienes and lipoxines broadly regulate innate and acquired immunity, and their dysfunction causes various immune-mediated disorders. We previously reported a salient feature of arachidonate 5-lipoxyganase (Alox5), which is responsible for the production of such lipid mediators, in the regulation of high affinity antibodies in vivo. The aim of this study was to determine the functional significance of Alox5-related lipid mediators during the processes of acquired humoral responses.

Functional RNAs control T follicular helper cells.

T follicular helper cells (Tfh cells), which are a prototypic subset of effector CD4 T cells, regulate the production of high-affinity antibodies by controlling B cells at initial and recall phases. Since the discovery of Tfh cells in human tonsils, many notable studies focusing on Tfh cells have clarified mechanisms underlying Tfh-cell-related physiological and pathological settings. Results of these studies revealed a chief regulatory function of BCL6 in Tfh cells and the involvement of Tfh cells in the pathogenesis of various disorders including autoimmune diseases, allergies and cancers.

Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation.

Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown.

Bob1 limits cellular frequency of T-follicular helper cells.

T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1.

Oral administration of the Aureobasidium pullulans-derived β-glucan effectively prevents the development of high fat diet-induced fatty liver in mice.

Aureobasidium pullulans-derived β-glucan (AP-PG) consisting of a β-(1,3)-linked glucose main chain and β-(1,6)-linked glucose branches is taken as a supplement to improve health. This study demonstrates that oral administration of AP-PG is effective to prevent the development of high-fat diet (HFD)-induced fatty liver in mice. Here, C57BL/6N mice were fed with a normal diet or HFD, and AP-PG diluted in drinking water was administered orally.

Stimulation of macrophages with the β-glucan produced by aureobasidium pullulans promotes the secretion of tumor necrosis factor-related apoptosis inducing ligand (TRAIL).

A β-glucan produced by Aureobasidium pullulans (AP-PG) is consisting of a β-(1,3)-linked main chain with β-(1,6)-linked glucose side residues. Various β-glucans consisting of β-(1,3)-linked main chain including AP-PG are believed to exhibit anti-tumor activities, and actually, anti-tumor activities of AP-PG in mice have been demonstrated. In this study, we demonstrate that stimulation with AP-PG induces TRAIL expression in mouse and human macrophage-like cell lines.

Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma.

Allergic rhinitis (AR), the most common allergic disorder of the airway, is often accompanied by bronchial asthma. However, little is known about the mechanism by which AR advances to AR comorbid with bronchial asthma (AR+Asthma). To determine the pathophysiologic features of AR and AR+Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR+Asthma patients.

ΔNp63 controls a TLR3-mediated mechanism that abundantly provides thymic stromal lymphopoietin in atopic dermatitis.

In the skin lesions of atopic dermatitis (AD), keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP), causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP.

Stimulation with the Aureobasidium pullulans-produced β-glucan effectively induces interferon stimulated genes in macrophage-like cell lines.

A β-(1,3),(1,6)-D-glucan produced by A. pullulans (AP-PG) is known to be an immune stimulating agent. In this study, we demonstrate that the stimulation with AP-PG effectively induces the interferon (IFN) stimulated genes (ISGs) in macrophage-like cell lines.

β-Glucan derived from Aureobasidium pullulans is effective for the prevention of influenza in mice.

β-(1→3)-D-glucans with β-(1→6)-glycosidic linked branches produced by mushrooms, yeast and fungi are known to be an immune activation agent, and are used in anti-cancer drugs or health-promoting foods. In this report, we demonstrate that oral administration of Aureobasidium pullulans-cultured fluid (AP-CF) enriched with the β-(1→3),(1→6)-D-glucan exhibits efficacy to protect mice infected with a lethal titer of the A/Puerto Rico/8/34 (PR8; H1N1) strain of influenza virus. The survival rate of the mice significantly increased by AP-CF administration after sublethal infection of PR8 virus.

A small scale study on the effects of oral administration of the β-glucan produced by Aureobasidium pullulans on milk quality and cytokine expressions of Holstein cows, and on bacterial flora in the intestines of Japanese black calves.

Background: The β-(1 → 3),(1 → 6)-D-glucan extracellularly produced by Aureobasidium pullulans exhibits immunomodulatory activity, and is used for health supplements. To examine the effects of oral administration of the β-(1 → 3),(1 → 6)-D-glucan to domestic animals, a small scale study was conducted using Holstein cows and newborn Japanese Black calves.

Findings: Holstein cows of which somatic cell count was less than 3 x 10⁵/ml were orally administered with or without the β-(1 → 3),(1 → 6)-D-glucan-enriched A.

RelE-mediated dormancy is enhanced at high cell density in Escherichia coli.

Bacteria show remarkable adaptability under several stressful conditions by shifting themselves into a dormant state. Less is known, however, about the mechanism underlying the cell transition to dormancy. Here, we report that the transition to dormant states is mediated by one of the major toxin-antitoxin systems, RelEB, in a cell density-dependent manner in Escherichia coli K-12 MG1655.

In vitro toxicity of silver nanoparticles at noncytotoxic doses to HepG2 human hepatoma cells.

Although it has been reported that silver nanoparticles (Ag-NPs) have strong acute toxic effects to various cultured cells, the toxic effects at noncytotoxic doses are still unknown. We, therefore, evaluated in vitro toxicity of Ag-NPs at noncytotoxic doses in human hepatoma cell line, HepG2, based on cell viability assay, micronucleus test, and DNA microarray analysis. We also used polystyrene nanoparticles (PS-NPs) and silver carbonate (Ag2CO3) as test materials to compare the toxic effects with respect to different raw chemical composition and form of silver.

Increased antibiotic resistance of Escherichia coli in mature biofilms.

Biofilms are considered to be highly resistant to antimicrobial agents. Several mechanisms have been proposed to explain this high resistance of biofilms, including restricted penetration of antimicrobial agents into biofilms, slow growth owing to nutrient limitation, expression of genes involved in the general stress response, and emergence of a biofilm-specific phenotype. However, since combinations of these factors are involved in most biofilm studies, it is still difficult to fully understand the mechanisms of biofilm resistance to antibiotics.

Localized expression profiles of rpoS in Escherichia coli biofilms.

Although importance of the rpoS gene on biofilm formation by Escherichia coli has been suggested, there has not been any report showing where the rpoS is expressed during biofilm formation process. Since physiological state of the cells in the biofilms is considerably heterogeneous, the expression of the rpoS gene must be heterogeneous. In this study, in situ spatial expression of the rpoS gene during biofilm formation was investigated with an rpoS-gfp transcriptional fusion mutant strain.

Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis.

Carcinogenesis is an important chronic toxicity of metals and metalloids, although their mechanisms of action are still unclear. Comparison of gene expression patterns induced by carcinogenic metals, metalloids, and model carcinogens would give an insight into understanding of their carcinogenic mechanisms. In this study, we examined the gene expression alteration in human hepatoma cell line, HepG2, after exposing to two metals (cadmium and nickel), a metalloid (arsenic), and three model carcinogenic chemicals N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA), and tetrachloroethylene (TCE) using DNA microarrays with 8,795 human genes.

Significance of rpoS during maturation of Escherichia coli biofilms.

Presence of starved, stationary phase-like zones in biofilms seems to be an important factor for biofilm formation. In this study, roles of rpoS gene in the formation of Escherichia coli biofilms were investigated. E.

Classification of heavy-metal toxicity by human DNA microarray analysis.

Microarray technology is proving to be a useful tool to classify undefined environmental toxicants, to investigate underlying mechanisms of toxicity, and to identify candidate toxicant-specific genetic markers by examining global effects of putative toxicants on gene expression profiles. The aim of this study was to evaluate the toxicities of six heavy metals through the comparison with gene expression patterns induced by well-known chemicals. For this purpose, we first identified the genes altered specifically in HepG2 under the exposure of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), phenol, and N-nitrosodimethylamine (DMN), which were selected as the model chemicals, using DNA microarray.