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[PMID]:29339155
[Au] Autor:Kuwabara J; Umakoshi A; Abe N; Sumida Y; Ohsumi S; Usa E; Taguchi K; Choudhury ME; Yano H; Matsumoto S; Kunieda T; Takahashi H; Yorozuya T; Watanabe Y; Tanaka J
[Ad] Endereço:Department of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
[Ti] Título:Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a novel Wistar rat metastasis model.
[So] Source:Biochem Biophys Res Commun;496(2):542-548, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The results showed that 100% of rats with C6-L tumors developed lung metastases, while metastases were found in only 44% of rats with C6-S tumors (n = 25). Tumors disappeared in approximately 20% of the C6-S-bearing rats, and these animals evaded death 180 d after transplantation, while all C6-L tumor-bearing rats died after 45 d. Next generation sequencing revealed that C6-S tumors expressed chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry revealed that C6-S tumors contained more dead cells and more CD45 cells, including natural killer cells and CD8 lymphocytes. In particular, multiple subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were more abundant in C6-S than in C6-L tumors. These results suggested that CD200S induced the accumulation of multiple dendritic cell subsets that activated cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells.
[Mh] Termos MeSH primário: Antígenos CD/imunologia
Glioma/imunologia
Glioma/patologia
Neoplasias Pulmonares/imunologia
Neoplasias Pulmonares/secundário
[Mh] Termos MeSH secundário: Animais
Antígenos CD/genética
Células Dendríticas/imunologia
Células Dendríticas/patologia
Regulação Neoplásica da Expressão Gênica
Glioma/genética
Tolerância Imunológica
Imunidade Celular
Pulmão/imunologia
Pulmão/patologia
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Mutação
Ratos Wistar
Linfócitos T Citotóxicos/imunologia
Linfócitos T Citotóxicos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (antigens, CD200)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


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[PMID]:29337391
[Au] Autor:Ishii T; Niikura Y; Kurata K; Muroi M; Tanamoto K; Nagase T; Sakaguchi M; Yamashita N
[Ad] Endereço:Department of Pharmacotherapy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
[Ti] Título:Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite-induced asthma mouse model.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:House dust mites (HDMs) are a common source of allergens that trigger both allergen-specific and innate immune responses in humans. Here, we examined the effect of allergen concentration and the involvement of Toll-like receptor 4 (TLR4) in the process of sensitization to house dust mite allergens in an HDM extract-induced asthma mouse model. Intranasal administration of HDM extract induced an immunoglobulin E response and eosinophilic inflammation in a dose-dependent manner from 2.5 to 30 µg/dose. In TLR4-knockout mice, the infiltration of eosinophils and neutrophils into the lung was decreased compared with that in wild-type mice in the early phase of inflammation (total of three doses). However, in the late phase of inflammation (total of seven doses), eosinophil infiltration was significantly greater in TLR4-knockout mice than in wild-type mice. This suggests that the roles of TLR4 signaling are different between the early phase and the later phase of HDM allergen-induced inflammation. Thus, innate immune response through TLR4 regulated the response to HDM allergens, and the regulation was altered during the phase of inflammation.
[Mh] Termos MeSH primário: Alérgenos/imunologia
Antígenos de Dermatophagoides/imunologia
Asma/imunologia
Imunidade Inata/imunologia
Pyroglyphidae/imunologia
Receptor 4 Toll-Like/imunologia
[Mh] Termos MeSH secundário: Resistência das Vias Respiratórias/imunologia
Animais
Líquido da Lavagem Broncoalveolar/citologia
Modelos Animais de Doenças
Eosinófilos/patologia
Feminino
Imunização
Imunoglobulina E/imunologia
Inflamação/imunologia
Pulmão/citologia
Pulmão/imunologia
Pulmão/patologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Infiltração de Neutrófilos/imunologia
Neutrófilos/patologia
Transdução de Sinais/imunologia
Receptor 4 Toll-Like/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Antigens, Dermatophagoides); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); 37341-29-0 (Immunoglobulin E)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12641


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[PMID]:29337059
[Au] Autor:Lin L; Li M; Lin L; Xu X; Jiang G; Wu L
[Ad] Endereço:Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Tongji University School of Medicine, Shanghai 200092, China.
[Ti] Título:FPPS mediates TGF-ß1-induced non-small cell lung cancer cell invasion and the EMT process via the RhoA/Rock1 pathway.
[So] Source:Biochem Biophys Res Commun;496(2):536-541, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, was recently shown to play a role in cancer progression. However, its role in non-small cell lung cancer (NSCLC) metastasis and the underlying mechanism remain unclear. In this study, FPPS expression was significantly correlated with TNM stage, and metastasis. Inhibition or knockdown of FPPS blocked TGF-ß1-induced cell invasion and epithelial-to-mesenchymal transition (EMT) process. FPPS expression of FPPS was induced by TGF-ß1 and FPPS promoted cell invasion and EMT via the RhoA/Rock1 pathway. In conclusion, FPPS mediates TGF-ß1-induced lung cancer cell invasion and EMT via the RhoA/Rock1 pathway. These findings suggest new treatment strategies to reduce mortality associated with metastasis in patients with NSCLC.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Transição Epitelial-Mesenquimal
Geraniltranstransferase/metabolismo
Neoplasias Pulmonares/metabolismo
Fator de Crescimento Transformador beta1/metabolismo
Quinases Associadas a rho/metabolismo
Proteína rhoA de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Idoso
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/patologia
Linhagem Celular Tumoral
Feminino
Regulação Neoplásica da Expressão Gênica
Geraniltranstransferase/análise
Geraniltranstransferase/genética
Seres Humanos
Pulmão/metabolismo
Pulmão/patologia
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Masculino
Meia-Idade
Invasividade Neoplásica/genética
Invasividade Neoplásica/patologia
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Transforming Growth Factor beta1); EC 2.5.1.10 (Geranyltranstransferase); EC 2.7.11.1 (ROCK1 protein, human); EC 2.7.11.1 (rho-Associated Kinases); EC 3.6.5.2 (rhoA GTP-Binding Protein)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:28459622
[Au] Autor:Martinez CH; Murray S; Barr RG; Bleecker E; Bowler RP; Christenson SA; Comellas AP; Cooper CB; Couper D; Criner GJ; Curtis JL; Dransfield MT; Hansel NN; Hoffman EA; Kanner RE; Kleerup E; Krishnan JA; Lazarus SC; Leidy NK; O'Neal W; Martinez FJ; Paine R; Rennard SI; Tashkin DP; Woodruff PG; Han MK; Subpopulations and Intermediate Outcome Measures in COPD Study Investigators
[Ad] Endereço:1 Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan.
[Ti] Título:Respiratory Symptoms Items from the COPD Assessment Test Identify Ever-Smokers with Preserved Lung Function at Higher Risk for Poor Respiratory Outcomes. An Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort.
[So] Source:Ann Am Thorac Soc;14(5):636-642, 2017 May.
[Is] ISSN:2325-6621
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Ever-smokers without airflow obstruction scores greater than or equal to 10 on the COPD Assessment Test (CAT) still have frequent acute respiratory disease events (exacerbation-like), impaired exercise capacity, and imaging abnormalities. Identification of these subjects could provide new opportunities for targeted interventions. OBJECTIVES: We hypothesized that the four respiratory-related items of the CAT might be useful for identifying such individuals, with discriminative ability similar to CAT, which is an eight-item questionnaire used to assess chronic obstructive pulmonary disease impact, including nonrespiratory questions, with scores ranging from 0 to 40. METHODS: We evaluated ever-smoker participants in the Subpopulations and Intermediate Outcomes in COPD Study without airflow obstruction (FEV /FVC ≥0.70; FVC above the lower limit of normal). Using the area under the receiver operating characteristic curve, we compared responses to both CAT and the respiratory symptom-related CAT items (cough, phlegm, chest tightness, and breathlessness) and their associations with longitudinal exacerbations. We tested agreement between the two strategies (κ statistic), and we compared demographics, lung function, and symptoms among subjects identified as having high symptoms by each strategy. RESULTS: Among 880 ever-smokers with normal lung function (mean age, 61 yr; 52% women) and using a CAT cutpoint greater than or equal to 10, we classified 51.8% of individuals as having high symptoms, 15.3% of whom experienced at least one exacerbation during 1-year follow-up. After testing sensitivity and specificity of different scores for the first four questions to predict any 1-year follow-up exacerbation, we selected cutpoints of 0-6 as representing a low burden of symptoms versus scores of 7 or higher as representing a high burden of symptoms for all subsequent comparisons. The four respiratory-related items with cutpoint greater than or equal to 7 selected 45.8% participants, 15.6% of whom experienced at least one exacerbation during follow-up. The two strategies largely identified the same individuals (agreement, 88.5%; κ = 0.77; P < 0.001), and the proportions of high-symptoms subjects who had severe dyspnea were similar between CAT and the first four CAT questions (25.9% and 26.8%, respectively), as were the proportions reporting impaired quality of life (66.9% and 70.5%, respectively) and short walking distance (22.4% and 23.1%, respectively). There was no difference in area under the receiver operating characteristic curve to predict 1-year follow-up exacerbations (CAT score ≥10, 0.66; vs. four respiratory items from CAT ≥7 score, 0.65; P = 0.69). Subjects identified by either method also had more depression/anxiety symptoms, poor sleep quality, and greater fatigue. CONCLUSIONS: Four CAT items on respiratory symptoms identified high-risk symptomatic ever-smokers with preserved spirometry as well as the CAT did. These data suggest that simpler strategies can be developed to identify these high-risk individuals in primary care.
[Mh] Termos MeSH primário: Progressão da Doença
Pulmão/fisiopatologia
Doença Pulmonar Obstrutiva Crônica/fisiopatologia
Fumar/fisiopatologia
[Mh] Termos MeSH secundário: Idoso
Biomarcadores
Estudos Transversais
Feminino
Volume Expiratório Forçado
Seres Humanos
Estudos Longitudinais
Masculino
Meia-Idade
Avaliação de Resultados (Cuidados de Saúde)
Estudos Prospectivos
Qualidade de Vida
Curva ROC
Índice de Gravidade de Doença
Fumar/efeitos adversos
Espirometria
Inquéritos e Questionários
Estados Unidos
Capacidade Vital
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Biomarkers)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1513/AnnalsATS.201610-815OC


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[PMID]:29231024
[Au] Autor:Yao J; Kan WJ
[Ad] Endereço:Institute of Forensic Science, Nantong Public Security Bureau, Nantong 226007, China.
[Ti] Título:[Diatom Detection Using Enzyme Combined with Strong Acid Digestion Method].
[So] Source:Fa Yi Xue Za Zhi;33(2):165-167, 2017 Apr.
[Is] ISSN:1004-5619
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVES: To detect diatom in the organs of drowners by enzyme combined with strong acid digestion method, and evaluate its application value. METHODS: A total of 40 cases which have been identified as drowning in local region were collected. Samples of the lung, liver, kidney, and the water of the scene were also gathered from each case. Strong acid digestion method, enzyme combined with strong acid digestion method, and enzymic digestion method were respectively performed to detect the diatom in the samples. The comparative analysis was made on digestion time, digestive power and detection rate of diatom, etc. RESULTS: Enzyme combined with strong acid digestion method was significantly better than enzymic digestion method on digestion time and digestive power; enzyme combined with strong acid digestion method were obviously superior to strong acid digestion method on the detection rate of diatom. CONCLUSIONS: Enzyme combined with strong acid digestion method combines the advantages of strong acid digestion method and enzymic digestion method. It has the characters of operation safety with little pollution to environment, which is worthy of further popularization and practice.
[Mh] Termos MeSH primário: Diatomáceas/isolamento & purificação
Afogamento
Rim/metabolismo
Fígado/metabolismo
Pulmão/metabolismo
[Mh] Termos MeSH secundário: Patologia Legal/métodos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.3969/j.issn.1004-5619.2017.02.012


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[PMID]:29204997
[Au] Autor:Zhao B; Yao SQ; Hao XH
[Ad] Endereço:Forensic Science Brigade of Tangshan Public Security Bureau, Tangshan 063000, China.
[Ti] Título:[Expression of AQP-1 and AQP-4 in the Lungs of Drown Rats].
[So] Source:Fa Yi Xue Za Zhi;32(5):321-325, 2016 Oct.
[Is] ISSN:1004-5619
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVES: To observe the changes of expression of aquaporin-1(AQP-1) and AQP-4 in drowned and postmortem immersed rats' lungs. METHODS: Thirty healthy male Wistar rats were randomly divided into drowning group, postmortem immersion group and cervical dislocation group. The morphological changes of rats' lungs were observed using HE staining. The mRNA and protein expressions of AQP-1 and AQP-4 in rats' lungs were detected by real-time PCR, immunohistochemistry and Western blotting, respectively. RESULTS: The results of immunohistochemistry and the Western blotting showed that the protein expression of AQP-1 of the drowning group was higher than the postmortem immersion group and the cervical dislocation group ( <0.05). The result of immunohistochemistry showed that the protein expression of AQP-4 of the drowning group was higher than the postmortem immersion group and the cervical dislocation group ( <0.05) while no difference were detected among the three of them by Western blotting ( >0.05). The mRNA expressions of AQP-1 and AQP-4 in rats' lungs of the drowning group was significantly higher than the postmortem immersion group ( <0.05). CONCLUSIONS: The increase of mRNA and protein expressions of AQP-1 and AQP-4 in lungs of rats with cute lung injury of the drowning group would be useful for differentiating vital drowning from postmortem immersion.
[Mh] Termos MeSH primário: Aquaporina 1/metabolismo
Aquaporina 4/metabolismo
Afogamento
Pulmão/metabolismo
[Mh] Termos MeSH secundário: Animais
Autopsia
Western Blotting
Imuno-Histoquímica
Masculino
RNA Mensageiro
Ratos
Ratos Sprague-Dawley
Ratos Wistar
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aqp1 protein, rat); 0 (Aqp4 protein, rat); 0 (Aquaporin 4); 0 (RNA, Messenger); 146410-94-8 (Aquaporin 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.3969/j.issn.1004-5619.2016.05.001


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[PMID]:28453808
[Au] Autor:Kobayashi N; Kobayashi K; Kikuchi S; Goto Y; Ichimura H; Endo K; Sato Y
[Ad] Endereço:Department of General Thoracic Surgery, Tsukuba University Hospital, Tsukuba, Ibaraki, Japan.
[Ti] Título:Long-term pulmonary function after surgery for lung cancer.
[So] Source:Interact Cardiovasc Thorac Surg;24(5):727-732, 2017 05 01.
[Is] ISSN:1569-9285
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Many patients with lung cancer have been cured by surgical intervention. However, the long-term effects of lung resection on pulmonary function are unclear. Therefore, we investigated long-term pulmonary function after surgery. METHODS: We retrospectively reviewed the medical records of patients who underwent surgery for lung cancer between 2001 and 2009. A total of 445 patients who had survived more than 5 years since the surgery were included. The patients were divided into lobectomy, segmentectomy and partial resection groups. The time-dependent changes in pulmonary function were investigated. RESULTS: The percentages of the vital capacity and forced expiratory volume in 1 second (FEV 1 ) at postoperative year (POY) 1 vs preoperative values were 92.9 ± 11.1% and 91.3 ± 13.0% in the lobectomy group, 95.9 ± 9.0% and 93.8 ± 10.5% in the segmentectomy group and 97.8 ± 7.3% and 98.1 ± 8.3% in the partial resection group, respectively. The values in the lobectomy group were significantly lower than those in the segmentectomy and partial resection groups. The percentages of vital capacity and FEV 1 at POY 5 vs preoperative values were 90.0 ± 11.5% and 86.2 ± 11.9% in the lobectomy group, 93.4 ± 9.8% and 91.1 ± 9.8% in the segmentectomy group and 94.3 ± 8.8% and 94.0 ± 8.0% in the partial resection group, respectively. The decrease in the rates from POY 1 to POY 5 were not significantly different among the procedures. CONCLUSIONS: Pulmonary function declined with pulmonary resection. After the patient recovered from the operation, pulmonary function decreased with time regardless of the surgical procedure.
[Mh] Termos MeSH primário: Volume Expiratório Forçado/fisiologia
Neoplasias Pulmonares/cirurgia
Pulmão/fisiopatologia
Pneumonectomia/métodos
Capacidade Vital/fisiologia
[Mh] Termos MeSH secundário: Idoso
Feminino
Seguimentos
Seres Humanos
Pulmão/cirurgia
Neoplasias Pulmonares/fisiopatologia
Masculino
Período Pós-Operatório
Testes de Função Respiratória
Estudos Retrospectivos
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/icvts/ivw414


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[PMID]:29237524
[Au] Autor:Li L; Chen Q; Zhang F; Zhu SG; Hu CL; Wu AM
[Ad] Endereço:Department of Respiration, Jiangxi Children's Hospital, Nanchang 330000, China. nclilan@163.com.
[Ti] Título:[Characteristics of tidal breathing pulmonary function in children with tracheobronchomalacia].
[So] Source:Zhongguo Dang Dai Er Ke Za Zhi;19(12):1248-1251, 2017 Dec.
[Is] ISSN:1008-8830
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To investigate the characteristics of tidal breathing pulmonary function in children with tracheobronchomalacia (TBM). METHODS: In this study, 30 children who were diagnosed with TBM using electronic bronchoscopy were enrolled in the observation group; 30 healthy children were recruited in the normal control group. For individuals in each group, the assessment of tidal breath pulmonary function was performed at diagnosis and 3, 6, 9, and 12 months after diagnosis. RESULTS: There were no significant differences in tidal volume, inspiratory time, expiratory time, and inspiratory to expiratory ratio between the two groups (P>0.05). Compared with the control group, the observation group had a significantly higher respiratory rate and significantly lower ratio of time to peak tidal expiratory flow to total expiratory time (TPTEF/TE) and ratio of volume to peak tidal expiratory flow to total expiratory volume (VPTEF/VE). There was a time-dependent increase in TPTEF/TE and VPTEF/VE for TBM children from the time of initial diagnosis to 12 months after diagnosis. CONCLUSIONS: Tidal breathing pulmonary function has characteristic changes in children with TBM. Tidal breathing pulmonary function tends to be recovered with increased age in children with TBM.
[Mh] Termos MeSH primário: Pulmão/fisiopatologia
Respiração
Volume de Ventilação Pulmonar
Traqueobroncomalácia/fisiopatologia
[Mh] Termos MeSH secundário: Fatores Etários
Feminino
Seres Humanos
Lactente
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE


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[PMID]:28747346
[Au] Autor:Nagalingam G; Vinuesa CG; Britton WJ; Saunders BM
[Ad] Endereço:Tuberculosis Research Program, Centenary Institute, Newtown, New South Wales 2042, Australia.
[Ti] Título:Modulation of Roquin Function in Myeloid Cells Reduces -Induced Inflammation.
[So] Source:J Immunol;199(5):1796-1804, 2017 09 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Damaging inflammation is a hallmark of infection, and understanding how this is regulated is important for the development of new therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is involved in immune regulation; however, its role in immunity to is unknown. To address this, we infected mice with a point mutation in ( ). Aerosol-infected mice showed enhanced control of infection associated with delayed bacterial dissemination and upregulated TNF production in the lungs after 2 wk. However, this early control of infection was not maintained, and by 8 wk postinfection mice demonstrated an increased bacterial burden and dysregulated inflammation in the lungs. As the inflammation in the lungs of the mice could have been influenced by emerging autoimmune conditions that are characteristic of the mice aging, the function of Roquin was examined in immune cell subsets in the absence of autoimmune complications. bacillus Calmette-Guérin-primed T cells transferred into mice provided equivalent protection in the spleen and liver. Interestingly, the transfer of mycobacteria-specific (P25 CD4 TCR transgenic) wild-type spleen cells into mice actually led to enhanced protection with reduced bacterial load, decreased chemokine expression, and reduced inflammation in the lungs compared with transfers into mice expressing intact Roquin. These studies suggest that modulation of Roquin in myeloid cells may reduce both inflammation and bacterial growth during the chronic phase of infection.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Inflamação/imunologia
Pulmão/imunologia
Mycobacterium tuberculosis/fisiologia
Células Mieloides/imunologia
Tuberculose/imunologia
Ubiquitina-Proteína Ligases/metabolismo
[Mh] Termos MeSH secundário: Animais
Carga Bacteriana
Linfócitos T CD4-Positivos/microbiologia
Linfócitos T CD4-Positivos/transplante
Células Cultivadas
Pulmão/microbiologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Células Mieloides/microbiologia
Quimeras de Transplante
Fator de Necrose Tumoral alfa/metabolismo
Ubiquitina-Proteína Ligases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Tumor Necrosis Factor-alpha); EC 2.3.2.27 (Rc3h1 protein, mouse); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1602069


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[PMID]:28742815
[Au] Autor:Xu J; Guardado J; Hoffman R; Xu H; Namas R; Vodovotz Y; Xu L; Ramadan M; Brown J; Turnquist HR; Billiar TR
[Ad] Endereço:Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
[Ti] Título:IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model.
[So] Source:PLoS Med;14(7):e1002365, 2017 Jul.
[Is] ISSN:1549-1676
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury. METHODS AND FINDINGS: Blunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling. Dynamic changes in IL33 and soluble suppression of tumorigenicity 2 (sST2) levels were measured in the plasma and correlated with levels of the type 2 cytokines and nosocomial infection. Based on the observations in humans, mechanistic experiments were designed in a mouse model of resuscitated hemorrhagic shock and tissue trauma (HS/T). These experiments utilized wild-type C57BL/6 mice, IL33-/- mice, B6.C3(Cg)-Rorasg/sg mice deficient in group 2 innate lymphoid cells (ILC2), and C57BL/6 wild-type mice treated with anti-IL5 antibody. Severely injured human blunt trauma patients (n = 472, average injury severity score [ISS] = 20.2) exhibited elevations in plasma IL33 levels upon admission and over time that correlated positively with increases in IL4, IL5, and IL13 (P < 0.0001). sST2 levels also increased after injury but in a delayed manner compared with IL33. The increases in IL33 and sST2 were significantly greater in patients that developed nosocomial infection and organ dysfunction than similarly injured patients that did not (P < 0.05). Mechanistic studies were carried out in a mouse model of HS/T that recapitulated the early increase in IL33 and delayed increase in sST2 in the plasma (P < 0.005). These studies identified a pathway where IL33 induces ILC2 activation in the lung within hours of HS/T. ILC2 IL5 up-regulation induces further IL5 expression by CXCR2+ lung neutrophils, culminating in early lung injury. The major limitations of this study are the descriptive nature of the human study component and the impact of the potential differences between human and mouse immune responses to polytrauma. Also, the studies performed did not permit us to make conclusions about the impact of IL33 on pulmonary function. CONCLUSIONS: These results suggest that IL33 may initiate early detrimental type 2 immune responses after trauma through ILC2 regulation of neutrophil IL5 production. This IL33-ILC2-IL5-neutrophil axis defines a novel regulatory role for ILC2 in acute lung injury that could be targeted in trauma patients prone to early lung dysfunction.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica
Imunidade Humoral
Interleucina-33/metabolismo
Interleucina-5/genética
Linfócitos/imunologia
Ferimentos e Lesões/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Estudos de Coortes
Modelos Animais de Doenças
Feminino
Seres Humanos
Interleucina-33/sangue
Interleucina-5/imunologia
Pulmão/imunologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Meia-Idade
Estudos Retrospectivos
Choque Hemorrágico/complicações
Choque Hemorrágico/imunologia
Ferimentos e Lesões/etiologia
Ferimentos e Lesões/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL33 protein, human); 0 (Il33 protein, mouse); 0 (Interleukin-33); 0 (Interleukin-5)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pmed.1002365



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