Different doses of ovalbumin exposure on dendritic cells determine their genetic/epigenetic regulation and T cell differentiation.

It has been reported that allergen dosage can impact the differentiation of dendritic cells (DCs)-mediated T cells. However, the mechanisms of such dose-dependent differentiation are poorly understood. In this study, bone marrow-derived immature DCs stimulated with Ovalbumin (OVA) of different concentrations (0, 10, 100, 1000, 10000µg/ml, respectively). DCs were then co-cultured with naïve T cells. RNA-sequencing detection and DNA methylation of DCs were performed. We show that when DCs were stimulated with low-dose (10µg/ml), 77 genes were up-regulated and 87 genes down-regulated. Most activated genes were related to ribosome synthesis and ion channel inhibition. At the medium-dose (100µg/ml), 339 genes were up-regulated and 168 genes down-regulated. Most activated genes involved cytokine synthesis and regulation of immune responses. At high-dose (10000µg/ml), 2497 genes were up-regulated and 1156 genes down-regulated. TNF signaling pathway, NF-kappa B signaling pathway, antigen processing and presentation signaling pathway were mostly up-regulated. The related co-stimulators, co-inhibitory molecules, inhibitory cytokines, negative regulating enzymes were highly expressed. The monocarbate, coenzyme, fatty acid, glucolipid, starch, sucrose and other metabolism-related signaling pathways were down-regulated. The profiles of DNA methylation and RNA synthesis of DCs varied with different doses of OVA, which serves to induce T cells to differentiate in various directions.

The Comparation of Intraperitoneal Injection and Nasal-only Delivery Allergic Rhinitis Model Challenged With Different Allergen Concentration.

BACKGROUND: Predominantly, 2 animal models are used for allergic rhinitis (AR), which are established by intraperitoneal (IP) injection plus local challenge and nasal-only delivery. The differences between these 2 models are not fully understood. Moreover, dose-response relationship to allergens remains unclear. METHODS: In this study, mice were sensitized by nasal drops (without adjuvant, once daily for 9 weeks) to set up a nasal-only delivery AR model. Five different doses of ovalbumin (OVA) nasal drops were served to explore the dose-response to allergens. Allergic symptoms, serum antibodies (IgE, IgG2a, and IgG1), spleen supernatant and nasal lavage fluid (NALF) cytokines (IL-4, IL-5, and IFN-r), and infiltrated eosinophils of the nasal mucosa were observed. RESULTS: The allergic symptoms, serum antibodies, cytokines, and infiltrated eosinophils were significantly higher in the high OVA concentration compared with those of the control group. Different OVA concentrations associated with the severity of allergy. Within a certain concentration range, OVA concentration positively related to the severity of symptoms, IgE antibody level, and Th2 bias. Meanwhile, serum antibodies (IgE and IgG1) and cytokines (IL-4, IL-5 in spleen and IL-4 in NALF) were significantly higher in the classical IP injection group than in the nasal drip groups. CONCLUSION: The IP injection model and the nasal-only delivery model are 2 typical models for AR that causes a different immune response. A positive dose-response relationship in the nasal-only delivery model is observed from 25 mg/mL to 0.025 mg/mL.

[Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a Meta-analysis of the efficacy and safety].

OBJECTIVE: To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer. METHOD: Literature about the efficacy and safety of Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis. RESULT: A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group. CONCLUSION: The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.

Maternofetal transfer of antibodies and the influence of maternal atopic status on the neonate.

BACKGROUND: Epidemiologic evidence has shown that sensitization of allergic diseases develops early in life, even before birth. The gestational environment, including maternal atopic status and transplacentally transferred antibodies to allergens, may be of importance in the sensitization process. OBJECTIVE: To investigate maternofetal transfer of antibodies and the influence of maternal atopic status on the neonatal immune response. METHODS: Fifty-seven healthy pregnant women who underwent elective cesarean section (ECS) were recruited. Total and specific IgE (Phadiatop) levels in cord blood (CB) and maternal blood (MB) were determined using the ImmunoCAP assay. MB- and CB-specific IgG1 and IgA1 antibodies against ovalbumin and house dust mite were analyzed by enzyme linked immunosorbent assay. The cytokines, interleukin (IL)-13, interferon (IFN)-γ, and IL-10 in the supernatant of cultured CB mononuclear cells were quantified by enzyme linked immunosorbent assay. Two subgroups were defined based on the maternal levels of specific IgE (atopic group, Phadiatop IgE more than or equal to 0.35 kilo international units of allergen-specific antibody (KUA)/L; nonatopic group, Phadiatop IgE less than 0.35 KUA/L). RESULTS: Although total IgE was detectable in all MB samples, it could only be detected in 7% (4/57) of the CB samples. Specific IgE was detectable in all MB samples but undetectable in all CB samples. There was no correlation of total IgE between mothers and their neonates. The concentrations of IL-10, IL-13, and allergen-specific IgG1 and IgA1 in the CB samples did not differ significantly between the atopic and nonatopic groups. IFN-γ was undetectable in the CB samples. CONCLUSIONS: Maternal IgE cannot be transferred to the child in utero. Maternal atopic status has no significant effect on neonatal immune responses.

House dust mite allergen levels in households and correlation with allergic rhinitis symptoms.

BACKGROUND: House dust mite (HDM) allergen is a risk factor for the development of allergic rhinitis (AR). OBJECTIVES: To determine the levels of indoor allergens in the households of patients with AR in Wuhan city, identify the environmental risk factors for high allergen exposure, and investigate the correlations between allergen exposure and specific immunoglobulin E levels and symptoms. METHODS: The study examined 50 patients with AR. Two dust samples were collected from the bedding of each patient, one in summer and one in winter. Major allergens Der p 1 and Der f 1, from Dermatophagoides pteronyssinus and Dermatophagoides farinae, were measured with an enzyme-linked immunosorbent assay. Participants completed a standardized questionnaire about their living environments, and their rhinitis symptom scores were calculated. Specific immunoglobulin E levels against Der p and Der f were measured. RESULTS: The percentage of bedding samples with high HDM allergen (Der f 1 + Der p 1) levels (>10 µg/g) was 44% in summer and 46% in winter. There was no significant difference between the level of mite allergens in summer and winter; however, the level of Der f 1 was higher than that of Der p 1 (p < 0.05). The age of the mattress and pillow was significantly correlated with allergen concentration. Indoor HDM allergen level affected the severity of nasal itching. CONCLUSIONS: HDMs are important indoor allergens in Wuhan. Mattresses and pillows that have been used for a long time contain high levels of allergens. High levels of exposure to HDM allergens correlates with the severity of nasal itching.

[Meta-analysis of association between MMP-1-1607 polymorphism and head and neck cancer risk in asia population].

OBJECTIVE: To analyze and explore the association between the 1607(1G/2G) single nucleotide polymorphism (SNP) in promoter of matrix metalloproteinase-1 (MMP-1) gene and susceptibility of head and neck cancer (HNC) by Meta-analysis. METHOD: By the end of January 2014, the published literatures were collected for the case-control studies evaluating the relationship between HNC and -1607 SNP of MMP-1 gene from English and Chinese literature databases according to the inclusion and exclusion criteria. Then the meta-analysis, the heterogeneity, bias and sensitivity of the results of the eligible literatures were conducted by Stata 10. 0. RESULT: A total of 9 studies including 2049 patients with HNC and 2158 controls were extracted for systematic review on the association of MMP-1 (-1607) 1G/2G SNP with the risk of HNC. Meta-analysis which based on random effects model showed that MMP-1 (-1607) 1G/2G SNP can significantly increase the risk of HNC[1G2G + 2G2G vs. 1G1G: OR = 1.45, 95% CI 1.25-1.68, P < 0.01; 2G2G vs. 1G1G + 1G2G:OR = 1.77, 95% CI 1.37-2.30, P < 0.01; 2G vs. 1G: OR = 1.52, 95% CI 1.26-1.85, P < 0.01; 2G2G vs. 1G1G: OR = 2.06, 95% CI 1.41-3.01, P < 0.01). CONCLUSION: MMP-1 (-1607) 1G/2G SNP has close relationship with HNC susceptibility, people who with 2G2G genotype carriers are susceptible to HNC.

[Effect of neonatal immunization with different dosage allergen on the immunity of mice when grown up].

OBJECTIVE: To study the effect of neonatal immunization with different dosage allergen on the immunity of mice when grown. METHODS: Fifty neonatal BALB/c mice were divided into 4 groups randomly and subcutaneous injected with different dosage of ovalbumin (OVA) on day 1, 8 and 15 after born [NS group(10): injected with saline alone; NS + AL group (10): injected with saline and AL(OH)3; small dosage (SD) group (15): injected with 10 microg OVA and AL(OH)3; large dosage (LD) group (15): injected with 1000 microg OVA and AL(OH)3]. The mice were then challenged using caudal vein injection on 5 weeks old (NS group and NS + AL group were challenged with saline, SD group and LD group were challenged with 100 microg OVA). The blood was collected 1 week later to examine OVA specific IgE, IgG1 and IgG2a. Mononuclear cells were drawn from the spleen and cultured. Concentration of IL-4, IFN-r, IL-10 was examined in the cultural supernatant. Flow cytometry was used to test the expression of CD4+ IL-4+, CD4+ IFN-gamma+, CD4 IL-10 cells. RESULTS: It was found that concentration of OVA specific IgE (OVA-sIgE) in SD group (0.33 +/- 0.18) was significantly higher than that of NS (0.07 +/- 0.01) and NS + AL (0.09 +/- 0.04) group (t value was -3.46 and -3.21, all P < 0.01), and LD group (0.17 +/- 0.10) as well (t = 2.58, P < 0.05). The concentration of OVA-sIgE was higher in LD group than that of NS group (t = -2.53, P < 0.05), but similar with that of NS + AL group (t = -2.04, P > 0.05). Both the concentration of OVA-sIgG1 and sIgG2a was higher in SD and LD group than that of NS and NS + AL group (all P < 0.05). The concentration of IL-4, IFN-gamma and IL-10 in the cultural supernatant of spleen mononuclear was all higher in SD group than that of NS and NS + AL group (all P < 0.01). The ratio of IFN-gamma/IL-4 was significantly lower in SD group than that of NS and NS + AL group (t value was 2.14, 3.44, all P < 0.05), while the same ratio was higher in LD group than that of NS and NS + AL group (t value was -2.14, -1.61, all P < 0.05). Ratio of CD4+ IL-4+ cells was significant lower in LD group than that of SD group (P < 0.05), while it was not different with that of NS and NS + AL group (P > 0. 05). CONCLUSION: Neonatal immunization with low dosage OVA could generate a specific immunity with Th2 direction, while with large dosage OVA could generate a specific immunity with Th1 direction.