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1.
J Allergy Clin Immunol ; 145(1): 402-414, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31647966

RESUMO

BACKGROUND: Epidemiologic evidence suggests that exposure to particulate matter of 2.5 µm or less in diameter (PM2.5) aggravates asthma. OBJECTIVE: We sought to investigate the underlying mechanisms between PM2.5 exposure and asthma severity. METHODS: The relationship between PM2.5 exposure and asthma severity was investigated in an asthma model with CD4+ T cell-specific aryl hydrocarbon receptor (AhR)-null mice. Effects of PM2.5 and polycyclic aromatic hydrocarbons (PAHs) on differentiation of TH17/regulatory T (Treg) cells were investigated by using flow cytometry and quantitative RT-PCR. Mechanisms were investigated by using mRNA sequencing, chromatin immunoprecipitation, bisulfite sequencing, and glycolysis rates. RESULTS: PM2.5 impaired differentiation of Treg cells, promoted differentiation of TH17 cells, and aggravated asthma in an AhR-dependent manner. PM2.5 and one of its prominent PAHs, indeno[1,2,3-cd]pyrene (IP), promoted differentiation of TH17 cells by upregulating hypoxia-inducible factor 1α expression and enhancing glycolysis through AhRs. Exposure to PM2.5 and IP enhanced glutamate oxaloacetate transaminase 1 (Got1) expression through AhRs and accumulation of 2-hydroxyglutarate, which inhibited ten-eleven translocation methylcytosine dioxygenase 2 activity, resulting in hypermethylation in the forkhead box P3 locus and impaired differentiation of Treg cells. A GOT1 inhibitor, (aminooxy)acetic acid, ameliorated asthma by shifting differentiation of TH17 cells to Treg cells. Similar regulatory effects of exposure to PM2.5 or IP on TH17/Treg cell imbalance were noted in human T cells, and in a case-control design PAH exposure appeared to be a potential risk factor for asthma. CONCLUSIONS: The AhR-hypoxia-inducible factor 1α and AhR-GOT1 molecular pathways mediate pulmonary responses on exposure to PM2.5 through their ability to disturb the balance of TH17/Treg cells.

2.
Chin Med J (Engl) ; 132(16): 1959-1964, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31373908

RESUMO

BACKGROUND: Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy. METHODS: Forty Hartley guinea pigs were divided into four groups according to the NiSO4 sensitizing concentration and the NiSO4 challenged concentration: the 5% NiSO4-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO4-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-µ-XRF) and micro X-ray absorption near-edge spectroscopy (µ-XANES). RESULTS: In each section, the nickel element concentration in both the 5% NiSO4-group and 10% NiSO4-group was significantly higher than that in the negative control group. In the upper 300-µm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (>200 µm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-µ-XRF. According to the XANES data for the 10% NiSO4 metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni aqueous ionic state but in the nickel-binding protein. CONCLUSIONS: This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.


Assuntos
Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/metabolismo , Níquel/metabolismo , Níquel/toxicidade , Espectrometria por Raios X/métodos , Animais , Dermatite Alérgica de Contato/patologia , Feminino , Cobaias , Masculino , Distribuição Aleatória , Pele/metabolismo , Pele/patologia
3.
Clin Rev Allergy Immunol ; 57(1): 128-143, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31243705

RESUMO

Allergen immunotherapy (AIT) for allergic rhinitis (AR), asthma, and other allergic diseases has developed quickly. House dust mite (HDM), Artemisia (wormwood), Humulus japonicus (Japanese hop), Alternaria alternata, and Cladosporium herbarum are the five most common inhalant allergens in China. AIT has been performed in China for over 60 years. With the support of the Chinese Medical Association (CMA) and the Chinese Medical Doctors Association (CMDA), the Chinese College of Allergy and Asthma (CCAA) was established in 2016 as a specialized branch of CDMA and is the main certification authority for AIT. Chinese allergists and scientists have made tremendous progress in the development of AIT. There have been many publications by Chinese allergists and scientists worldwide encompassing original research studies, systematic reviews, case studies, and clinical trials. Currently, conventional subcutaneous immunotherapy (SCIT) is the preferred AIT in China, but sublingual immunotherapy (SLIT) is beginning to gain recognition. An increasing number of clinical trials have been conducted to investigate the clinical efficacy and side effects of SLIT and SCIT. In China, HDM is the only commercial standardized allergen extracts in clinical use, whereas the others are crude allergen extracts. Besides standardized allergen extracts, other forms of hypoallergenic extracts are still being investigated and developed in China. Immunotherapy in China is similar to that in the USA in which allergen extracts can be mixed for SCIT. However, allergen extracts cannot be mixed for SCIT in Europe.


Assuntos
Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Rinite Alérgica/epidemiologia , Rinite Alérgica/terapia , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Adulto , Alérgenos/imunologia , Animais , Asma/terapia , Criança , Pré-Escolar , China , Humanos , Lactente , Recém-Nascido , Exposição por Inalação , Camundongos , Prevalência , Pyroglyphidae/imunologia , Imunoterapia Sublingual/efeitos adversos , Estados Unidos , Vacinas de DNA/uso terapêutico
4.
Clin Transl Allergy ; 9: 28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31139345

RESUMO

Background: The identification of house dust mite (HDM) allergens and epitopes is important for allergy diagnosis and treatment. We sought to identify the Dermatophagoides pteronyssinus group 24 allergen (Der p 24) and to identify its immunodominant IgE epitope(s). Methods: Der p 24 cDNA was cloned and expressed in a pET expression system. The IgE binding activity of purified recombinant (r)Der p 24 was evaluated by western blotting. Truncated Der p 24 proteins and overlapping synthetic polypeptides were subjected to IgE binding assays. Balb/c mice were immunized to investigate IgE epitope induction of IgE production. IgE binding of the 32 N-terminal residues of Der p 24 was compared to other Der p epitopes in enzyme-linked immunosorbent assays and dot blot assays. Human skin prick tests (SPTs) were performed. Results: We cloned and expressed Der p 24 cDNA (GenBank accession no. KP893174.1). HDM allergic sera bound rDer p 24 in vitro and 5/10 HDM allergic patients (50%) had positive SPT reactions to rDer p 24. The immunodominant IgE epitope of Der p 24 was localized to the N-terminal 32-residue region, which produced a high specific IgE antibody titer in vivo and promoted mast cell ß-hexosaminidase release. The IgE binding activity this N-terminal epitope of Der p 24 was stronger than that of Der p 1 or Der p 2 IgE epitopes. Conclusions: We identified Der p 24 as a major HDM allergen with strong IgE binding activity via an immunodominant IgE epitope in the N-terminal 32-residue region, which triggers IgE production in vivo. The identified Der p 24 epitope may support HDM allergy diagnosis and treatment.

5.
Curr Microbiol ; 76(5): 590-596, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30859288

RESUMO

Nickel, a silver-colored metal found in nature, is a common cause of allergic contact dermatitis. Nevertheless, the existence of inflammatory reaction to oral nickel exposure remains controversial. The following study investigates whether oral nickel can change the intestinal microflora in mice. A total of 20 female ICR mice were randomly divided into two groups: the oral nickel group (Group O) and the control group (Group C). Group O received water containing 400 µM NiSO4·6H2O, while group C was given pure water for 21 days. The content of nickel in the kidneys was determined by atomic absorption spectrophotometry, while the composition of bacterial community in the cecum was detected by 16S rDNA sequencing. The results were subsequently validated by real-time quantitative PCR with genus and species specific primers. Compared to Group C, significantly higher nickel levels were observed in Group O (P = 0.016); however, our data suggested that oral administration of 400 µM NiSO4·6H2O was nontoxic to the animals. (No statistical difference in body animal weight was found between Group O and Group C, before and after oral administration of nickel.) At the genus level, significantly higher relative abundance of Bacteroides (P = 0.016) and Intestinimonas (P = 0.018), and significantly lower relative abundance of Lachnospiraceae_NK4A136_group (P = 0.002) and Lachnospiraceae_UCG-001_group (P = 0.042) were observed in the oral nickel group compared to the control group. In addition, Group O had significantly lower ratio of Firmicutes/Bacteroides (P = 0.008). The results of real-time quantitative PCR further confirmed that the amplicon mass of Bacteroides and B. fragilis in the Group O was significantly higher compared to C group (P = 0.034 and P = 0.02). Oral nickel could change the intestinal microflora in mice, thus suggesting that oral nickel alters the interaction between the host and the intestinal flora.


Assuntos
Bactérias/classificação , Microbioma Gastrointestinal/efeitos dos fármacos , Níquel/administração & dosagem , Administração Oral , Animais , Bactérias/efeitos dos fármacos , Bacteroides/efeitos dos fármacos , Ceco/microbiologia , Feminino , Rim/química , Camundongos , Camundongos Endogâmicos ICR , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real , Espectrofotometria Atômica
6.
Int J Mol Med ; 43(3): 1531-1541, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664181

RESUMO

Dogs are a major source of indoor allergens. However, the prevalence of dog allergies in China remains unclear, especially in children. In the present study, Can f 7, a canine allergen belonging to the Niemann pick type C2 protein family, was selected to study its sensitization rate in Chinese children with dog allergies. The Can f 7 gene was subcloned into a pET­28a vector and expressed in Escherichia coli BL21 (DE3) cells. Recombinant Can f 7 was purified by nickel affinity chromatography, identified by SDS­PAGE electrophoresis, and had its allergenicity assessed by western blot, ELISA and basophil activation tests. Through a series of bioinformatical approaches, B­cell epitopes, secondary structures, and 3 dimensional (3D) homology modeling of Can f 7 were predicted. The activity of the B cell epitopes was verified by ELISA. The recombinant Can f 7 showed a distinct band with a molecular weight of 14 kDa. Six of 20 sera from dog­allergic children reacted positively to the Can f 7. Can f 7 induced an ~4.0­fold increase in cluster of differentiation 63 and C­C motif chemokine receptor R3 expression in basophils sensitized with the serum of dog­allergic children compared with those of non­allergic controls. The secondary structure analysis showed that Can f 7 contains 6 ß­sheets. Five B cell epitopes of Can f 7 were predicted, and two of these were confirmed by ELISA. These results indicate that Can f 7 is an important canine allergen in Chinese children and provide novel data for further research concerning the use of Can f 7 in the diagnosis and treatment of Chinese children with canine allergy symptoms.


Assuntos
Alérgenos/genética , Alérgenos/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Expressão Gênica , Lipocalinas/genética , Lipocalinas/imunologia , Adolescente , Alérgenos/química , Alérgenos/isolamento & purificação , Sequência de Aminoácidos , Animais , Criança , Pré-Escolar , Códon , Cães , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito B/química , Feminino , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Lactente , Lipocalinas/química , Lipocalinas/isolamento & purificação , Masculino , Modelos Moleculares , Conformação Proteica , Proteínas Recombinantes
7.
Clin Rev Allergy Immunol ; 57(1): 98-110, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30612248

RESUMO

The prevalence of food allergies is increasing worldwide. To understand the regional specificities of food allergies and develop effective therapeutic interventions, extensive regional epidemiological studies are necessary. While data regarding incidence, prevalence, regional variation, and treatment in food allergies are available for western countries, such studies may not be available in many Asian countries. China accounts for almost 20% of the world's population and has a vast ethnic diversity, but large-scale meta-analyses of epidemiological studies of food allergy in China are lacking. A literature search revealed 22 publications on the prevalence of food allergy in Chinese populations. A review of these studies showed that the prevalence of food allergies in China is comparable to that in western countries, even though the Chinese diet is vastly different from that of the West and may vary even greatly within China, and finally, specific antigenic triggers of food allergy vary between China and the West and also within China. Current clinical management of food allergy in China includes allergen-specific immunotherapy, Chinese herbal medicine, acupuncture, and Western medicine. This study demonstrates an unmet need in China for a thorough investigation of the prevalence of food allergies in China, the specific foods involved, and characterization of the specific antigenic triggers of food allergy with respect to ethnicity, age, and diet in China.


Assuntos
Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/terapia , Adolescente , Animais , Criança , Pré-Escolar , China/epidemiologia , Cidades/epidemiologia , Dessensibilização Imunológica , Dieta , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Imunoglobulina E/imunologia , Incidência , Lactente , Recém-Nascido , Masculino , Medicina Tradicional Chinesa , Camundongos , Omalizumab/imunologia , Omalizumab/uso terapêutico , Prevalência
8.
Chin Med J (Engl) ; 131(21): 2583-2588, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30381592

RESUMO

Background: Sublingual immunotherapy (SLIT) has been proven to be effective against house dust mite-induced allergic rhinitis. However, the efficacy in adults with allergic rhinitis has never been reported on SLIT tablets. The current meta-analysis aimed to illustrate the differentiated efficacy of SLIT tablets on allergic rhinitis. Methods: Our systematic review and meta-analysis were performed on allergic rhinitis patients and aimed to summarize those randomized controlled studies (RCTs). PubMed, EMBASE, Cochrane library, and MEDLINE were screened for associated articles. We included RCTs on allergic rhinitis patients undergoing SLIT therapy and reporting outcomes on symptom relief and serum-specific IgE levels. The effect of SLIT tablets on the Rhinitis Quality Life Questionnaire Score (RQLQ), Rhinitis Total Symptom Score (RTSS), and serum-specific IgE levels was evaluated using RevMan 5.3. Results: Seven studies were included, with 2723 patients identified. All of the studies were RCT. The included seven studies were all conducted on adults. Among the included seven articles, five researches administered patients with SLIT tablets and were eligible for meta-analysis of RTSS, consisting of 1490 patients. Overall, RTSS was significantly reduced in the SLIT tablet group compared with that in the placebo group (standard mean difference = -0.33, 95% confidence interval [-0.54, -0.13], P < 0.01). There was no significant difference in specific IgE levels between SLIT and placebo patients. Conclusions: SLIT tablets effectively relieve rhinitis symptoms in adults with allergic rhinitis. Nevertheless, the current evidence may be limited due to sample size and the heterogeneity between studies. Large sample size and multiple center RCTs on the efficacy of different formulations of SLIT drugs are still needed to provide further evidence and a more precise recommendation.


Assuntos
Rinite Alérgica/terapia , Imunoterapia Sublingual/métodos , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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