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1.
Comput Biol Med ; 128: 104126, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33260035

RESUMO

Genes act in groups known as gene modules, which accomplish different cellular functions in the body. The modular nature of gene networks was used in this study to detect functionally enriched modules in samples obtained from COPD patients. We analyzed modules extracted from COPD samples and identified crucial genes associated with the disease COVID-19. We also extracted modules from a COVID-19 dataset and analyzed a suspected set of genes that may be associated with this deadly disease. We used information available for two other viruses that cause SARS and MERS because their physiology is similar to that of the COVID-19 virus. We report several crucial genes associated with COVID-19: RPA2, POLD4, MAPK8, IRF7, JUN, NFKB1, NFKBIA, CD40LG, FASLG, ICAM1, LIFR, STAT2 and CCR1. Most of these genes are related to the immune system and respiratory organs, which emphasizes the fact that COPD weakens this system and makes patients more susceptible to developing severe COVID-19.


Assuntos
/genética , Bases de Dados de Ácidos Nucleicos , Predisposição Genética para Doença , Doença Pulmonar Obstrutiva Crônica/genética , /genética , /imunologia , Humanos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/virologia , Índice de Gravidade de Doença
2.
Life Sci ; 265: 118864, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33301808

RESUMO

Beta-2 adrenergic receptors (ß2-ARs) have important roles in the pathogenesis and treatment of chronic obstructive pulmonary disease (COPD). In recent years, progress has been made in the study of ß2-ARs. Here, we introduce the basic concepts of ß2-ARs, related pathways, as well as application of blockers/agonists of ß2-ARs, and ß2-AR autoantibodies in COPD. Drugs targeting the ß2-AR are being developed rapidly, and we expect them to improve the symptoms and prognosis of COPD patients in the future.


Assuntos
Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Receptores Adrenérgicos beta 2/metabolismo , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Autoanticorpos/imunologia , Desenvolvimento de Medicamentos , Humanos , Prognóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/imunologia , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Receptores Adrenérgicos beta 2/imunologia
3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(11): 961-966, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33210588

RESUMO

Objective To analyze the differentially expressed genes (DEGs) in alveolar macrophages (AMs) of patients with chronic obstructive pulmonary disease (COPD) and their potential roles in the pathogeneses of COPD using bioinformatics. Methods Gene chip and RNA sequencing data sets of AMs in patients with COPD were downloaded from GEO. Limma and Degseq2 packages in R software were applied to obtain DEGs, and the GO enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction analysis (PPI), and the hub gene analysis were performed to predict the molecular mechanisms of DEGs. Results Through the integration of three data sets, a total of 43 DEGs of AMs were obtained, and the function predictive analysis found that the 43 DEGs were primarily related to chemokines, cytokines, complement, cytochrome P450, etc., which mainly included the significantly low expression of C-X-C motif chemokine ligand 9 (CXCL9), CXCL11, etc. and the significantly high expression of cytochrome P450 family 1 subfamily B member 1 (CYP1B1). Conclusion The DEGs of AMs in patients with COPD are related to the molecular mechanisms of immunity and inflammation and might be involved in the pathogenesis of chronic inflammation of COPD.


Assuntos
Perfilação da Expressão Gênica , Macrófagos Alveolares , Doença Pulmonar Obstrutiva Crônica , Biologia Computacional , Humanos , Macrófagos Alveolares/imunologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Software
4.
Med Hypotheses ; 144: 110284, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33245278

RESUMO

In the context of the current SARS-CoV-2 pandemic, patients affected by chronic obstructive pulmonary disease (COPD) should be more vulnerable to Covid-19, whereas they seem to be protected against severe Covid-19. That paradox has important practical implications for the use of the drug Tocilizumab in Covid-19. Interleukin-6 (IL-6) orchestrates the so-called cytokine storm leading to the Acute Respiratory Distress Syndrome (ARDS), the life-threatening condition that is responsible for Covid-19 deaths. However, IL-6 has a paradoxical effect in many viral infections. For pathogens such as HIV and Hepatitis B for example, high elevations show a toxic effect and are associated with higher mortality (e.g. they promote progression to AIDS in HIV patients), whereas mild elevations show a protective effect. IL-6 can be therefore considered as being both a pro-inflammatory and an anti-inflammatory cytokine. Several studies have shown that severe COPD is associated with extremely-high levels of IL-6, whereas mild COPD is associated with mild elevations of IL-6. It is plausible that the chronic, mildly-elevated concentrations of IL-6 found in mild COPD patients is protective against the deterioration of Covid-19, as it is the case for other viral diseases. That may explain why COPD is surprisingly an uncommon comorbidity in Covid-19 intensive care units. This may have an important practical implication for the treatment of Covid-19 patients: our hypothesis is that Tocilizumab must be used exclusively in patients with an ongoing cytokine storm. Otherwise, an early use of Tocilizumab can be harmful, especially in patients affected by COPD or other conditions with mildly-elevated IL-6.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , /imunologia , Interleucina-6/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/imunologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Infecções por HIV/complicações , Hepatite B/complicações , Humanos , Inflamação , Modelos Teóricos , Doença Pulmonar Obstrutiva Crônica/complicações , /virologia , Resultado do Tratamento
5.
Sci Rep ; 10(1): 15287, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943702

RESUMO

Th17/Treg imbalance contributes to chronic obstructive pulmonary disease (COPD) development and progression. However, intracellular signaling by suppressor of cytokine signaling (SOCS) 1 and SOCS3 and the proteins signal transducer and activator of transcription (STAT) 3 and STAT5 that orchestrate these imbalances are currently poorly understood. Thus, these proteins were investigated in C57BL/6 mice after exposure to cigarette smoke (CS) for 3 and 6 months. The expression of interleukin was measured by ELISA and the density of positive cells in peribronchovascular areas was quantified by immunohistochemistry. We showed that exposure to CS in the 3rd month first induced decreases in the numbers of STAT5+ and pSTAT5+ cells and the expression levels of TGF-ß and IL-10. The increases in the numbers of STAT3+ and pSTAT3+ cells and IL-17 expression occurred later (6th month). These findings corroborate the increases in the number of SOCS1+ cells in both the 3rd and 6th months, with concomitant decreases in SOCS3+ cells at the same time points. Our results demonstrated that beginning with the initiation of COPD development, there was a downregulation of the anti-inflammatory response mediated by SOCS and STAT proteins. These results highlight the importance of intracellular signaling in Th17/Treg imbalance and the identification of possible targets for future therapeutic approaches.


Assuntos
Citocinas/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Transdução de Sinais/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Progressão da Doença , Regulação para Baixo/imunologia , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/imunologia , Proteína 1 Supressora da Sinalização de Citocina/imunologia , Proteína 3 Supressora da Sinalização de Citocinas/imunologia
7.
Sci Rep ; 10(1): 12796, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732964

RESUMO

Cigarette smoke exposure (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD). Macrophages have an important role in COPD because they release pro-inflammatory and anti-inflammatory cytokines. The present study's we investigate the functional changes in macrophages and monocytes exposed to cigarette smoke extract (CSE). Herein, using human monocyte-derived macrophages (MDMs) from healthy donors and we found that CSE was not associated with significant changes in the production of pro inflammatory cytokines by MDMs. In contrast, exposure to CSE suppressed the production of IL-6 and Gro-a/CXCL1 by LPS-stimulated-MDMs, but had an additive effect on the release of IL-8/CXCL8 and MCP1/CCL2. However, CSE exposure was associated with greater production, TARC/CCL-17 and CCL22/MDC. Moreover, MDMs displayed a lower uptake capacity after CSE exposure. We identify, for what is to our knowledge the first time that monocytes from patients with COPD produced less IL-8/CXCL8 and Gro-α/CXCL1 after LPS stimulation and produced higher levels of TARC/CCL17 and MDC/CCL-22 after IL-4 stimulation. Our present results highlighted a skewed immune response, with an imbalance in M1 vs. M2 cytokine production. In conclusion, exposure to CS has contrasting, multifaceted effects on macrophages and monocytes. Our data may provide a better understanding of the mechanisms underlying COPD.


Assuntos
Fumar Cigarros/efeitos adversos , Macrófagos/imunologia , Monócitos/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumaça/efeitos adversos , Tabaco/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fatores de Risco
8.
Life Sci ; 261: 118357, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32861794

RESUMO

In our previous study, T lymphocyte microparticles (TLMPs) originated from CEM T lymphoblast-like cell line induced enhanced production of inflammation-associated cytokines and apoptosis in human bronchial epithelial cells (HBEs). To measure TLMP subpopulations in bronchoalveolar lavage fluids (BALF) from patients with chronic obstructive pulmonary disease (COPD), and to explore the effects of MPs derived from different T cell subpopulations on airway epithelium, this study was conducted. A hospital-based case-control study including 47 COPD patients and 28 healthy volunteers was performed. The cellular origins of MPs from airway in COPD and controls were evaluated using flow cytometry. CD4+ or CD8+ TLMPs were isolated by MACS to investigate their effects on HBEs in vitro. The numbers of MPs derived from T lymphocytes in BALF as well as these subpopulations (CD4+ and CD8+ T lymphocytes) were significantly upregulated in COPD patients compared with healthy volunteers. However, there was no significant difference between stable COPD and patients with acute exacerbation. Additionally, significant correlation between CD4+ and CD8+ TLMPs was observed, however neither type nor total level of TLMPs was correlated with any base parameter. Furthermore, isolated CD4+ and CD8+ TLMPs reduced cell viability and induced significant production of inflammatory cytokines including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, MCP-2, matrix metallopeptidase (MMP)-9 and tumor necrosis factor-alpha (TNF-α) in HBEs, while the levels of anti-inflammatory cytokine IL-10 were decreased. TLMPs in the airways, as putative biomarkers, may lead to airway epithelial injury and inflammation and serve essential roles in the pathophysiology of COPD.


Assuntos
Micropartículas Derivadas de Células/imunologia , Epitélio/patologia , Pulmão/patologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Linfócitos T/imunologia , Idoso , Brônquios/patologia , Líquido da Lavagem Broncoalveolar , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Comunicação Celular , Citocinas/biossíntese , Progressão da Doença , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Cells ; 9(9)2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32847034

RESUMO

The preservation of cellular homeostasis requires the synthesis of new proteins (proteostasis) and organelles, and the effective removal of misfolded or impaired proteins and cellular debris. This cellular homeostasis involves two key proteostasis mechanisms, the ubiquitin proteasome system and the autophagy-lysosome pathway. These catabolic pathways have been known to be involved in respiratory exacerbations and the pathogenesis of various lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and coronavirus disease-2019 (COVID-19). Briefly, proteostasis and autophagy processes are known to decline over time with age, cigarette or biomass smoke exposure, and/or influenced by underlying genetic factors, resulting in the accumulation of misfolded proteins and cellular debris, elevating apoptosis and cellular senescence, and initiating the pathogenesis of acute or chronic lung disease. Moreover, autophagic dysfunction results in an impaired microbial clearance, post-bacterial and/or viral infection(s) which contribute to the initiation of acute and recurrent respiratory exacerbations as well as the progression of chronic obstructive and restrictive lung diseases. In addition, the autophagic dysfunction-mediated cystic fibrosis transmembrane conductance regulator (CFTR) immune response impairment further exacerbates the lung disease. Recent studies demonstrate the therapeutic potential of novel autophagy augmentation strategies, in alleviating the pathogenesis of chronic obstructive or restrictive lung diseases and exacerbations such as those commonly seen in COPD, CF, ALI/ARDS and COVID-19.


Assuntos
Autofagia/imunologia , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Progressão da Doença , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Infecções por Coronavirus/virologia , Fibrose Cística/imunologia , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Homeostase , Humanos , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/metabolismo , Lisossomos/metabolismo , Pandemias , Pneumonia Viral/virologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , /metabolismo
10.
Eur J Clin Invest ; 50(10): e13382, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32780415

RESUMO

In barely nine months, the pandemic known as COVID-19 has spread over 200 countries, affecting more than 22 million people and causing over than 786 000 deaths. Elderly people and patients with previous comorbidities such as hypertension and diabetes are at an increased risk to suffer a poor prognosis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although the same could be expected from patients with chronic obstructive pulmonary disease (COPD), current epidemiological data are conflicting. This could lead to a reduction of precautionary measures in these patients, in the context of a particularly complex global health crisis. Most COPD patients have a long history of smoking or exposure to other harmful particles or gases, capable of impairing pulmonary defences even years after the absence of exposure. Moreover, COPD is characterized by an ongoing immune dysfunction, which affects both pulmonary and systemic cellular and molecular inflammatory mediators. Consequently, increased susceptibility to viral respiratory infections have been reported in COPD, often worsened by bacterial co-infections and leading to serious clinical outcomes. The present paper is an up-to-date review that discusses the available research regarding the implications of coronavirus infection in COPD. Although validation in large studies is still needed, COPD likely increases SARS-CoV-2 susceptibility and increases COVID-19 severity. Hence, specific mechanisms to monitor and assess COPD patients should be addressed in the current pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Betacoronavirus , Biomassa , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Suscetibilidade a Doenças , Exposição Ambiental/estatística & dados numéricos , Predisposição Genética para Doença , Humanos , Pandemias , Material Particulado , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Índice de Gravidade de Doença , Fumaça , Fumar/epidemiologia , Fumar/imunologia
11.
Sci Rep ; 10(1): 12092, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694699

RESUMO

This study was to investigate the association between serum interleukin 32 (IL-32) concentration and clinical parameters in patients with stable chronic obstructive pulmonary disease (COPD). One hundred and sixteen patients with stable COPD and 70 healthy subjects were included in the study. The serum concentration of IL-32 was detected by enzyme-linked immunosorbent assay. The correlation between serum IL-32 and clinical parameters of patients with COPD was analyzed by T-test, one-way analysis of variance, multiple linear regression and receiver operating characteristic curve. The serum concentration of IL-32 in patients with stable COPD was higher than that in healthy control group (p < 0.001) and increased serum IL-32 was positively correlated with GOLD grading (p = 0.026), mMRC score (p = 0.004) and clinical medical history (p = 0.005), but negatively related to FEV1/FVC (p = 0.001) and FEV1% predicted (p = 0.001). Patient's COPD grading (p = 0.001), clinical medical history (p < 0.001) and FEV1/FVC (p = 0.001) exerted a significant impact on serum IL-32. The sensitivity and specificity of serum IL-32 for discerning COPD patients from healthy individuals were 85.34% and 64.29%, and the area under the curve was 0.808 (p < 0.001). Increased IL-32 is involved in the chronic disease progression of COPD, suggesting that IL-32 may be a molecular biomarker that reflects the severity of COPD and contributes to the disease diagnosis.


Assuntos
Biomarcadores/sangue , Interleucinas/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Regulação para Cima , Estudos de Casos e Controles , Proteínas de Ligação a DNA , Diagnóstico Precoce , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Transcrição
12.
Allergy ; 75(11): 2829-2845, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32496587

RESUMO

BACKGROUND: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. METHODS: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.


Assuntos
/imunologia , Basigina/imunologia , Doença Crônica/epidemiologia , Dipeptidil Peptidase 4/imunologia , /imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Asma/epidemiologia , Asma/genética , Asma/imunologia , Basigina/genética , /imunologia , Criança , Pré-Escolar , Comorbidade , Dipeptidil Peptidase 4/genética , Feminino , Expressão Gênica/genética , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Hipertensão/imunologia , Imunidade Inata/imunologia , Lactente , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/genética , Obesidade/imunologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Fatores de Risco , Adulto Jovem
14.
Niger J Clin Pract ; 23(6): 817-824, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525117

RESUMO

Background: The Global Initiative classification (GOLD) for chronic obstructive pulmonary disease (COPD), which relies on the practical issues of treatment of this complex and heterogeneous disease, may not be reliable in predicting disease severity and prognosis as the term of inflammation is excluded from the definition. Aim: The aim of this study was to determine systemic inflammatory markers in GOLD ABCD groups and to compare these parameters according to clinical and functional features. Methods: The study included 60 COPD patients and 59 healthy subjects. Comparisons were made with the pulmonary function test, transthoracic echocardiography and the six-minute walk test (6MWT). The COPD assessment test (CAT), modified Medical Research Council (mMRC), and index scores of body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) were recorded. The systemic inflammatory state was assessed using C-reactive protein, fibrinogen, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-18. Results: The levels of all serum inflammatory markers were higher in the COPD group than in the control group. TNF-α and IL-6 were significantly higher in the symptomatic groups (B and D) than in the less symptomatic groups (A and C) (P < 0.05). Spirometric parameters were more severe in Group D, followed by groups C, B and A, respectively. The 6MWT and the BODE scores were worst in Group D, followed by groups B, C and A. Conclusion: The results suggest that bronchodilator treatment alone might be insufficient in Group B patients, as the systemic inflammatory markers in addition to exercise capacity and mortality predictors were at the worst level in Groups D and B.


Assuntos
Biomarcadores/sangue , Mediadores da Inflamação/sangue , Inflamação/sangue , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Índice de Massa Corporal , Proteína C-Reativa , Estudos de Casos e Controles , Estudos Transversais , Dispneia/fisiopatologia , Ecocardiografia , Tolerância ao Exercício , Feminino , Humanos , Inflamação/imunologia , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Índice de Gravidade de Doença , Espirometria , Fator de Necrose Tumoral alfa/sangue , Teste de Caminhada
16.
Life Sci ; 256: 117829, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32454159

RESUMO

BACKGROUND: The development of Chronic Obstructive Pulmonary Disease (COPD) has been assessed and divided into slow development (SD), normal development (ND) and quick development (QD). Little is known about the plasma proteome characters among these three phenotypes. METHODS: We performed a comparative proteomic analysis in the plasma of normal control (NC), SD, ND and QD phenotype COPD patients using isobaric tags for relative and absolute quantitation (iTRAQ) technique. RESULTS: A total of 683 proteins were successfully identified in the plasma samples, of which 394 were considered as high-quality proteins (95% confidential peptides ≥ 2). Further, a total of 25, 19 and 27 different abundant proteins (DAPs) were identified in SD, ND and QD groups, respectively. Gene ontology (GO) classification analysis of all DAPs showed that immune system process (GO:0002376) were the most significant. The pathway enrichment analysis showed that innate immune response (GO:0045087), receptor-mediated endocytosis (GO:0006898) and proteolysis (GO:0006508) were the branch-end terms. Notably, the 15 QD special DAPs were considered as potential markers for identify patient might have quick development COPD, and thus provided more aggressive treatment strategy for these patients. CONCLUSION: This work provides an insight into global plasma proteome profiles among the SD, ND and QD phenotypes of COPD patients. The most significant GO terms that the DAPs enriched in were immune system related terms. In addition, the 15 QD specific DPAs provided candidates of potential markers to predict the development types of COPD patients.


Assuntos
Imunidade Inata/imunologia , Proteínas/metabolismo , Proteômica/métodos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Feminino , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Proteoma/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia
17.
Medicine (Baltimore) ; 99(16): e19537, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311923

RESUMO

BACKGROUND: The development of chronic obstructive pulmonary disease (COPD) is related to the T lymphocyte mediated inflammatory immune response and immune imbalance. The purpose of this systematic review was to evaluate the clinical efficacy and safety of acupoint application on T lymphocyte subsets in patients with COPD. METHODS: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, the Cochrane Library, and EMBASE for studies published as of Oct. 31, 2019. All randomized controlled trials of acupoint application on COPD patients that met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan5.3 software was used for meta-analysis. RESULTS: Eight studies (combined n = 524) qualified based on the inclusion criteria. Compared with routine treatment alone, acupoint application combined with routine treatment can significantly increase the T lymphocyte CD4/CD8 ratio (MD 0.12, 95% CI 0.03-0.21, P < .01, I = 49%), reduce CD8 T-cells (MD-0.99, 95% CI-1.70-0.28, P < .001, I = 37%), reduce the times of acute exacerbations (MD-0.28, 95% CI-0.35-0.21, P < .001, I = 0), and improve the clinical efficacy (MD 1.30, 95% CI 1.14-1.48, P < .001, I = 39%). CONCLUSION: Acupoint application can improve the CD4/CD8 ratio and CD8 T-cells in patients with COPD and has an auxiliary effect in reducing the times of acute exacerbations and improving clinical efficacy.


Assuntos
Pontos de Acupuntura , Terapias Complementares , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/imunologia , Administração Cutânea , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Terapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Immunity ; 52(4): 683-699.e11, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32294408

RESUMO

Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes. Tracheal cholinergic chemosensory cells expressed these genes, and genetic ablation of these cells abrogated peptide-driven stimulation of mucociliary clearance. Trpm5-deficient mice were more susceptible to infection with a natural pathogen, and formylated bacterial peptides were detected in patients with chronic obstructive pulmonary disease. Optogenetics and peptide stimulation revealed that ciliary beating was driven by paracrine cholinergic signaling from chemosensory to ciliated cells operating through muscarinic M3 receptors independently of nerves. We provide a cellular and molecular framework that defines how tracheal chemosensory cells integrate chemosensation with innate defense.


Assuntos
Acetilcolina/imunologia , Proteínas de Bactérias/farmacologia , Cílios/imunologia , Depuração Mucociliar/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Canais de Cátion TRPM/imunologia , Traqueia/imunologia , Acetilcolina/metabolismo , Animais , Proteínas de Bactérias/imunologia , Transporte Biológico , Cílios/efeitos dos fármacos , Cílios/metabolismo , Feminino , Formiatos/metabolismo , Expressão Gênica , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Optogenética/métodos , Comunicação Parácrina/imunologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/imunologia , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/imunologia , Canais de Cátion TRPM/deficiência , Canais de Cátion TRPM/genética , Papilas Gustativas/imunologia , Papilas Gustativas/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/patologia , Virulência
20.
Am J Respir Crit Care Med ; 202(4): 535-548, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32255375

RESUMO

Rationale: Emerging evidence supports a crucial role for tertiary lymphoid organs (TLOs) in chronic obstructive pulmonary disease (COPD) progression. However, mechanisms of immune cell activation leading to TLOs in COPD remain to be defined.Objectives: To examine the role of lung dendritic cells (DCs) in T follicular helper (Tfh)-cell induction, a T-cell subset critically implicated in lymphoid organ formation, in COPD.Methods: Myeloid cell heterogeneity and phenotype were studied in an unbiased manner via single-cell RNA sequencing on HLA-DR+ cells sorted from human lungs. We measured the in vitro capability of control and COPD lung DC subsets, sorted using a fluorescence-activated cell sorter, to polarize IL-21+CXCL13+ (IL-21-positive and C-X-C chemokine ligand type 13-positive) Tfh-like cells. In situ imaging analysis was performed on Global Initiative for Chronic Obstructive Lung Disease stage IV COPD lungs with TLOs.Measurements and Main Results: Single-cell RNA-sequencing analysis revealed a high degree of heterogeneity among human lung myeloid cells. Among these, conventional dendritic type 2 cells (cDC2s) showed increased induction of IL-21+CXCL13+ Tfh-like cells. Importantly, the capacity to induce IL-21+ Tfh-like cells was higher in cDC2s from patients with COPD than in those from control patients. Increased Tfh-cell induction by COPD cDC2s correlated with increased presence of Tfh-like cells in COPD lungs as compared with those in control lungs, and cDC2s colocalized with Tfh-like cells in TLOs of COPD lungs. Mechanistically, cDC2s exhibited a unique migratory signature and (transcriptional) expression of several pathways and genes related to DC-induced Tfh-cell priming. Importantly, blocking the costimulatory OX40L (OX40 ligand)-OX40 axis reduced Tfh-cell induction by control lung cDC2s.Conclusions: In COPD lungs, we found lung EBI2+ (Epstein-Barr virus-induced gene 2-positive) OX-40L-expressing cDC2s that induced IL-21+ Tfh-like cells, suggesting an involvement of these cells in TLO formation.


Assuntos
Células Dendríticas/imunologia , Pulmão/citologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/imunologia , Estruturas Linfoides Terciárias/etiologia , Idoso , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/imunologia
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