Interaction of Prevotella intermedia Strain 17 Leucine-Rich Repeat Domain Protein AdpF with Eukaryotic Cells Promotes Bacterial Internalization

Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells.     

Distinct B‐cell populations contribute to vaccine antigen‐specific antibody production in a transgenic mouse model

The generation of memory B cells by vaccination plays a critical role in maintaining antigen-specific antibodies and producing antibody responses upon re-exposure to a pathogen. B-cell populations contributing to antibody production and protection by vaccination remain poorly defined. We used influenza virus-like particle (VLP) vaccine in a transgenic mouse model that would identify germinal centre-derived memory B cells with the expression of yellow fluorescent protein (YFP⁺ cells). Immunization with influenza VLP vaccine did not induce significant increases in YFP⁺ cells although vaccine antigen-specific antibodies in sera were found to confer protection against a lethal dose of influenza A virus (A/PR8). In addition, CD43⁺ B220⁻ populations with low YFP⁺ cells mainly contributed to the production of vaccine antigen-specific IgG isotype-switched antibodies whereas CD43⁻ B220⁺ populations with high YFP⁺ cells were able to produce vaccine antigen-specific IgM antibodies. Challenge infection of immunized transgenic mice with live influenza A virus resulted in significant increases in YFP⁺ cells in the B220⁻ populations of spleen and bone marrow cells. These results suggest that CD43⁺ B220⁻ B cells generated by vaccination are important for producing influenza vaccine antigen-specific antibodies and conferring protection.     

Notch1 is an important mediator for enhancing of B‐cell activation and antibody secretion by Notch ligand

The roles of Notch1 and Notch2 in T‐cell function have been well studied, but the functional roles of Notch in B cells have not been extensively investigated, except for Notch2 involvement in peripheral marginal zone B‐cell differentiation. This study examined the roles of Notch1 in murine primary B cells. During B‐cell activation by B‐cell receptor ligation, Notch1 was up‐regulated while Notch2 was not. In addition, Notch1 up‐regulation itself did not contribute to the further activation of B cells, but the Notch ligand was important for Notch1‐mediated further B‐cell activation. Moreover, Notch1 deficiency significantly decreased B‐cell activation and antibody secretion under the presence of Notch ligand. These data suggest that Notch1 is an important mediator for enhancing B‐cell activation and antibody secretion by Notch ligand.     

Differential roles of hypothalamic serotonin receptor subtypes in the regulation of prolactin secretion in the turkey hen

In the turkey, exogenous serotonin (5-hydroxytryptamine, 5-HT) increases prolactin (PRL) secretion by acting through the dopaminergic (DAergic) system. In the present study, infusion of the 5-HT_2C receptor agonist, (R)(−)-DOI hydrochloride (DOI), into the third ventricle stimulates PRL secretion, whereas the 5-HT_1A receptor agonist, (+/−)-8-OH-DPAT hydrobromide (DPAT), inhibits PRL secretion. Using the immediate-early gene, c-fos, as an indicator of neuronal activity, in situ hybridization histochemistry showed preferential c-fos co-localization within tyrosine hydroxylase immunoreactive neurons (the rate limiting enzyme in DA synthesis) in the areas of the nucleus preopticus medialis (POM) and the nucleus premammillaris (PMM), in response to DPAT and DOI, respectively. To clarify the involvement of 5-HT_1A and 5-HT_2C receptors in PRL regulation, their mRNA expression was determined on hypothalamic tissue sections from birds in different reproductive stages. A significant difference in 5-HT_1A receptor was observed, with the POM of hypoprolactinemic short day and photorefractory birds showing the highest expression. 5-HT_2C receptors mRNA did not change during the reproductive cycle. The data presented support the notion that DA neurons in the PMM and POM mediate the stimulatory and inhibitory effects of 5-HT, respectively, on PRL secretion and the 5-HTergic system can both stimulate and inhibit PRL secretion.     

Effects of Transglutaminase 2 Inhibition on Ventilator-Induced Lung Injury

This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-κB (NF-κB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-κB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.

Graphical Abstract

相似文献   

Pertussis Seroprevalence in Korean Adolescents and Adults Using Anti-Pertussis Toxin Immunoglobulin G

This study was conducted to evaluate age-specific seroprevalence of pertussis in Korea and to formulate a strategy to prevent and reduce the incidence of pertussis. Residual serum samples of healthy adolescents and adults 11 yr of age or older were collected between July 2012 and December 2012, and anti-pertussis toxin (PT) IgG titers were measured using a commercial ELISA kit. We compared the mean anti-PT IgG titers and seroprevalence of pertussis of the six age groups: 11-20, 21-30, 31-40, 41-50, 51-60, and ≥ 61 yr. A total of 1,192 subjects were enrolled. The mean anti-PT IgG titer and pertussis seroprevalence were 35.53 ± 62.91 EU/mL and 41.4%, respectively. The mean anti-PT IgG titers and seroprevalence were not significantly different between the age groups. However, the seroprevalence in individuals 51 yr of age or older was significantly higher than in individuals younger than 51 yr (46.5% vs 39.1%, P = 0.017). Based on these results, a new pertussis prevention strategy is necessary for older adults.

Graphical Abstract

相似文献   

Clinicopathologic Analysis of Pituitary Adenoma: A Single Institute Experience

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke''s cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

Graphical Abstract

相似文献   

The Influence of Depression,Anxiety and Somatization on the Clinical Symptoms and Treatment Response in Patients with Symptoms of Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

This is the first study to investigate the influence of depression, anxiety and somatization on the treatment response for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). The LUTS/BPH patients were evaluated with the Korean versions of the International Prostate Symptom Score (IPSS), the Patient Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the PHQ-15. The primary endpoint was a responder rate defined by the total score of IPSS (≤ 7) at the end of treatment. The LUTS/BPH severity was significantly higher in patients with depression (whole symptoms P = 0.024; storage sub-symptom P = 0.021) or somatization (P = 0.024) than in those without, while the quality of life (QOL) was significantly higher in patients with anxiety (P = 0.038) than in those without. Anxious patients showed significantly higher proportion of non-response (odds ratio [OR], 3.294, P = 0.022) than those without, while somatic patients had a trend toward having more non-responders (OR, 2.552, P = 0.067). Our exploratory results suggest that depression, anxiety and somatization may have some influences on the clinical manifestation of LUTS/BPH. Further, anxious patients had a lower response to treatment in patients with LUTS/BPH. Despite of limitations, the present study demonstrates that clinicians may need careful evaluation of psychiatric symptoms for proper management of patients with LUTS/BPH.

Graphical Abstract

相似文献   

Impact of ENPP1 K121Q on Change of Insulin Resistance after Web-Based Intervention in Korean Men with Diabetes and Impaired Fasting Glucose

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We hypothesized that the difference in genotype may be one of the factors that affect the outcome of intervention. We genotyped 448 men with fasting glucose≥5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ) (13 CG and 64 IG). The web-based intervention based on a lifestyle modification was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated significantly decreased levels of fasting serum insulin (FSI) as compared to CG and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased, and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of covariance, K121Q did significantly influence the change of HbA1c in CG after appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR change (adjusted β=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q did not influence the change in IR. However, individuals with T2DM carrying the K121 variant are very responsive to the effect of BMI reduction on HOMA-IR.

Graphical Abstract

相似文献