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1.
Cytogenet Genome Res ; 159(2): 55-65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31630146

RESUMO

Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified. Here, we report a 47,XXY Chinese male with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) with regard to a Chinese male and a female control with normal karyotype by single-cell sequencing. A total of 24,439 cells were analyzed and divided into 5 immune cell types (including B cells, T cells, macrophage cells, dendritic cells, and natural killer cells) according to marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between the KS patient and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system and type I diabetes mellitus. Based on our data, we identified several candidate genes which may be implicated in regulating the phenotype of KS. Overall, this analysis provides a comprehensive map of the cell types of PBMCs in a KS patient at the single-cell level, which will contribute to the prevention of comorbidity and improvement of the life quality of KS patients.


Assuntos
Síndrome de Klinefelter/genética , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Genótipo , Humanos , Sistema Imunitário/imunologia , Infertilidade Masculina/genética , Infertilidade Masculina/imunologia , Síndrome de Klinefelter/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/fisiologia , Masculino , Fenótipo , Análise de Célula Única/métodos , Transcriptoma/genética , Transcriptoma/imunologia
2.
Mol Immunol ; 114: 278-288, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31419704

RESUMO

Protease-activated receptors (PARs) have been described in a wide diversity of vertebrate cells, including human immune cells. Macrophages are pivotal cells in the host-pathogen interaction and their polarization in M1 or M2 cells has been described as a new central paradigm in the immune response to pathogens. In this context, we explored the involvement of PAR activation by serine proteases on M1/M2 macrophage differentiation and their impact on the Th1/Th2 cytokine profile in response to Mycobacterium tuberculosis antigen. Our results demonstrate that the serine proteases, thrombin and trypsin, induce interleukin (IL)-4 release from human monocytes, together with upregulation of the macrophage mannose receptor (CD206) in the same way that alternative M2a differentiated cells with M-CSF/IL-4. Protease stimulation of monocytes in the presence of PAR-1 (SCH-79797) or PAR-2 (FSLLRY-NH2) antagonists abolished IL-4 release from monocytes, whereas the use of the peptide agonist for PAR-1 (SFLLRNPNDKYEPF-NH2) or PAR-2 (SLIGKV-NH2) induced the secretion of IL-4 at a level comparable to thrombin or trypsin. When these protease-induced M2 macrophages from healthy human PPD + donors were co-cultured with autologous lymphocyte population in the presence of Mycobacterium tuberculosis antigen, we found a consistent inhibition of IFN-γ/IL-12 release together with persistent IL-4 expression, in contrast to the expected Th1 profile obtained with M2a macrophages. To our knowledge, this is the first observation that proteolytic activation of PAR1/2 receptors in monocytes induces M2-like macrophages with impaired plasticity and their implication in the driving of the Th1/Th2 cytokine profile.


Assuntos
Polaridade Celular/fisiologia , Macrófagos/metabolismo , Macrófagos/fisiologia , Receptor PAR-1/metabolismo , Receptor PAR-2/metabolismo , Diferenciação Celular/fisiologia , Plasticidade Celular , Células Cultivadas , Citocinas/metabolismo , Humanos , Interleucina-4/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/fisiologia , Ativação de Macrófagos/fisiologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Monócitos/metabolismo , Monócitos/fisiologia , Mycobacterium tuberculosis/patogenicidade , Tripsina/metabolismo , Tuberculose/metabolismo , Regulação para Cima/fisiologia
3.
Allergol. immunopatol ; 47(4): 378-385, jul.-ago. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-186510

RESUMO

Introduction and objectives: Allergic asthma is a chronic inflammatory disorder of the airways. Th1, Th2 and Th17 cells are the main cells involved in the pathophysiology of asthma. The function of these cells is affected by T-bet, GATA3 and RORgammat transcription factors (respectively). Therefore, the aim of this study was to evaluate the effect of ginger (officinal Roscoe) extract on the expression of T-bet, GATA-3 and ROR-gamma in peripheral blood mononuclear cells (PBMC) of asthmatic patients, in comparison with healthy volunteers as controls. Materials and methods: In this case-control study, a total of 50 individuals including 25 patients with severe, moderate and mild allergic asthma and 25 unrelated healthy controls were involved. The PBMCs were isolated and divided into four groups: negative control, two positive controls (Budesonide and PHA) and ginger-extract treated group. After cell treatment and incubation for 48h, PBMCs were isolated and cDNA was synthesized. Gene expressions of T-bet, GATA3 and ROR-γt were evaluated by Real-time PCR. Results: According to the results of this study, hydroalcoholic extract of ginger could reduce the expression of GATA-3, ROR-gammat, and T-bet in PBMCs of asthmatic patients in comparison with untreated PBMCs (P values = 0.001, 0.001, and 0.002, respectively). It was also shown that the ginger extract could affect T-bet/GATA-3, T-bet/ROR-gamma, and ROR-gammat/GATA-3 expression ratios. Conclusions: This study showed that the use of ginger extract could control asthma and decrease the severity of this disease by affecting the main cells involving the symptoms of asthma in the airways


No disponible


Assuntos
Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Fator de Transcrição GATA3/metabolismo , Hipersensibilidade/tratamento farmacológico , Leucócitos Mononucleares/fisiologia , Extratos Vegetais/farmacologia , Proteínas com Domínio T/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Estudos de Casos e Controles , Fator de Transcrição GATA3/genética , Gengibre/imunologia , Regulação da Expressão Gênica , Proteínas com Domínio T/genética
4.
Acta Pharm ; 69(1): 75-86, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259717

RESUMO

Recent studies suggest that annexin A1 (ANXA1) promotes apoptosis in cancerous cells. This study aims to investigate the effects of ANXA1 on apoptosis and cell cycle arrest in K562, Jurkat and U937 cells and peripheral blood mononu-clear cells (PBMC). Cells were treated with ANXA1 and cyclophosphamide prior to flow cytometry analysis for apoptosis and cell cycle arrest induction. At 2.5µM, ANXA1 induced significant apoptosis in K562 (p ≤ 0.001) and U937 (p ≤ 0.05) cells, with EC50 values of 3.6 and 3.8 µM, respectively. In Jurkat cells, induction was not significant (EC50, 17.0 µM). No significant apoptosis induction was observed in PBMC. ANXA1 caused cycle arrest in the G0/G1 phase in K562 and U937 cells with p ≤ 0.001 for both, and (p ≤ 0.01) for Jurkat cells. ANXA1 induced apoptosis and cycle arrest in the G0/G1 phase in K562 and U937 cells, causing only cell cycle arrest in Jurkat cells.


Assuntos
Anexina A1/metabolismo , Apoptose/fisiologia , Pontos de Checagem do Ciclo Celular/fisiologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/fisiologia , Adolescente , Adulto , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Fase G1/fisiologia , Humanos , Células Jurkat , Células K562 , Masculino , Pessoa de Meia-Idade , Fase de Repouso do Ciclo Celular/fisiologia , Células U937 , Adulto Jovem
5.
Nat Commun ; 10(1): 2864, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253807

RESUMO

The T cell immune synapse is a site of intense vesicular trafficking. Here we show that the golgin GMAP210, known to capture vesicles and organize membrane traffic at the Golgi, is involved in the vesicular transport of LAT to the immune synapse. Upon activation, more GMAP210 interact with LAT-containing vesicles and go together with LAT to the immune synapse. Regulating LAT recruitment and LAT-dependent signaling, GMAP210 controls T cell activation. Using a rerouting and capture assay, we show that GMAP210 captures VAMP7-decorated vesicles. Overexpressing different domains of GMAP210, we also show that GMAP210 allows their specific delivery to the immune synapse by tethering LAT-vesicles to the Golgi. Finally, in a model of ectopic expression of LAT in ciliated cells, we show that GMAP210 tethering activity controls the delivery of LAT to the cilium. Hence, our results reveal a function for the golgin GMAP210 conveying specific vesicles to the immune synapse.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Complexo de Golgi/fisiologia , Leucócitos Mononucleares/fisiologia , Proteínas de Membrana/metabolismo , Proteínas Nucleares/metabolismo , Vesículas Transportadoras/fisiologia , Linhagem Celular , Proteínas do Citoesqueleto , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Proteínas Nucleares/genética , Proteínas R-SNARE/genética , Proteínas R-SNARE/metabolismo , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Transdução de Sinais , Linfócitos T/fisiologia
6.
Low Urin Tract Symptoms ; 11(4): 232-240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207098

RESUMO

OBJECTIVE: This study evaluated the effect of human umbilical cord blood mononuclear cells (HUCB-MNCs) on bladder dysfunction in streptozotocin (STZ; 35 mg/kg, i.v.)-induced diabetic rats. METHODS: Adult male Sprague-Dawley rats (n = 30) were equally divided into three groups: control group, STZ-diabetic group, and HUCB-MNC-treated group (1 × 106 cells). HUCB-MNCs were isolated by density gradient centrifugation from eight healthy donors and injected into the corpus cavenosum in STZ-diabetic rats 4 weeks after the induction of diabetes. Studies were performed 4 weeks after HUCB-MNC or vehicle injection. In vitro organ bath studies were performed on bladder strips, whereas protein expression of hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and α-smooth muscle actin (SMA) in the bladder and the ratio of smooth muscle cells (SMCs) to collagen were determined using western blotting and Masson trichrome staining. RESULTS: Neurogenic contractions of detrusor smooth muscle strips were 55% smaller in the diabetic group than control group (P < 0.05); these contractions were normalized by HUCB-MNC treatment. In addition, HUCB-MNC treatment restored the impaired maximal carbachol-induced contractile response in detrusor strips in the diabetic group (29%; P < 0.05). HUCB-MNC treatment improved the KCl-induced contractile response in the diabetic bladder (68%; P < 0.05), but had no effect on ATP-induced contractile responses. Increased expression of HIF-1α and VEGF protein and decreased expression of α-SMA protein and the SMC/collagen ratio in diabetic rats were reversed by HUCB-MNC. CONCLUSION: Administration of HUCB-MNCs facilitates bladder function recovery, which is likely related to downregulation of HIF-1α expression and attenuation of fibrosis in STZ-diabetic rats.


Assuntos
Diabetes Mellitus Experimental/complicações , Sangue Fetal/citologia , Leucócitos Mononucleares/fisiologia , Doenças da Bexiga Urinária/etiologia , Actinas/metabolismo , Animais , Western Blotting , Sangue Fetal/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Contração Muscular/fisiologia , Músculo Liso/fisiopatologia , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Biol Pharm Bull ; 42(6): 944-953, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155591

RESUMO

Leukocyte migration across the blood-brain barrier (BBB) is an important step in the progression of brain dysfunction in systemic inflammation. The purpose of this study was to identify the key regulatory molecule(s) at the BBB among the cluster of differentiation (CD) antigens involved in leucocyte migration in lipopolysaccharide (LPS)-induced systemic inflammation based on their absolute protein expressions. Here, we identified the absolute expression levels of 17 CD antigens in isolated brain capillaries (Bcap) of LPS-administered mice. Among them, the expression levels of CD54 and CD106 were dramatically increased in LPS-administered mice compared to the control by 6.21- and 3.67-fold, respectively. In peripheral blood mononuclear cells, the expression levels of CD11a/CD18, the counter-receptor for CD54, were similar to those of CD54 in Bcap of LPS-administered mice. On the other hand, the expression level of CD49d, part of CD29/CD49d complex, which is the counter-receptor for CD106, was under the limit of quantification. It is thus likely that CD54 at the BBB is predominantly involved in promoting leukocyte migration across the BBB in systemic inflammation. The expression levels of CD9, CD49c and CD97, which are thought to be involved in cell-to-cell interaction, were decreased by 40-60% in Bcap of LPS-administered mice. In contrast, the expression levels of 9 transporters, 2 receptors, and 1 tight junction-related protein in Bcap of LPS-administered mice were essentially unchanged compared to the control. These results suggest that enhancement of leucocyte migration in systemic inflammation involves dynamic changes of CD antigens without alterations of other major functional molecules.


Assuntos
Antígenos CD/imunologia , Barreira Hematoencefálica/imunologia , Encefalomielite Autoimune Experimental/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Animais , Movimento Celular , Feminino , Leucócitos Mononucleares/fisiologia , Lipopolissacarídeos/farmacologia , Masculino , Proteínas de Membrana Transportadoras/imunologia , Camundongos Endogâmicos C57BL
8.
Arch Virol ; 164(8): 2005-2013, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31102052

RESUMO

We previously found that genetic factors are associated with a familial predisposition for developing liver cirrhosis and hepatocellular carcinoma during chronic hepatitis B virus (HBV) infection. Autophagy has been shown to play a role in HBV replication and the course of disease. More than 190 host genes have been identified that modify the process of autophagy, but which of these genes are involved in chronicity of HBV infection and how this occurs remains unclear. Chronic hepatitis B (CHB) patients were recruited to investigate the expression of autophagy-modulating genes in peripheral blood mononuclear cells (PBMCs). mRNA prepared from PBMCs from members of two families with clustering HBV infection, including 11 CHB patients and nine healthy spouses, was hybridized to high-density oligonucleotide arrays. Immunoblot analysis was used to determine the level of autophagy. Of the 192 autophagy-modulating genes, 18 were found to be differently expressed. Of these, 11 displayed decreased expression in CHB patients, while seven displayed increased expression compared to those in healthy controls. Functional analysis showed that these genes are closely involved in initiation, nucleation, elongation of phagophores, formation of autophagosomes, transportation to lysosomes, and the process of degradation. Western blot analysis revealed inhibited autophagy in PBMCs based on decreased lipidation of LC3II. A differential expression profile of autophagy-modulating genes was observed, and decreased autophagy in PBMCs could be closely associated with chronicity of HBV infection, suggesting a novel strategy for the treatment of patients with chronic HBV infection.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Redes Reguladoras de Genes/genética , Hepatite B Crônica/genética , Leucócitos Mononucleares/fisiologia , Autofagossomos/fisiologia , Análise por Conglomerados , Feminino , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/virologia , Humanos , Lisossomos/fisiologia , Masculino , RNA Mensageiro/genética
9.
Vet Immunol Immunopathol ; 211: 35-37, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31084891

RESUMO

In mammals, the immune system is undergoing significant changes during development, which has many impacts on the individual's capacity to cope with infectious diseases or other pathologic conditions, where the immune system is involved. Especially in livestock, it is important to know in detail about these changes, including shifts in the composition of systemic leukocyte populations, as this knowledge may help to focus on relevant cell populations when developing novel vaccines for use in juvenile versus adult animals. In this mini-review, a synoptic comparison of published PBMC populations, which were analysed in healthy weaned piglets as well as multiparous non-gestating sows, shows remarkable shifts within leukocyte populations. γδ T cells increase by factor 1.5, plasmacytoid dendritic cells and T helper cells more than double, and cytotoxic T cells as well as regulatory T cells increase more than four fold, whereas NK cells as well as B cells in adult sows comprise only 40% and monocytes 70% of the relative population sizes in weaned piglets. In summary, these insights into age-dependent shifts of porcine leukocyte populations indicate a principal increase of acquired immunity-associated leukocyte populations, whereas primarily innate immunity-associated cell types (NK cells, monocytes) are diminished.


Assuntos
Envelhecimento/imunologia , Leucócitos Mononucleares/imunologia , Suínos/imunologia , Animais , Leucócitos Mononucleares/fisiologia , Suínos/sangue , Suínos/fisiologia
10.
Immunobiology ; 224(4): 497-501, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31133346

RESUMO

BACKGROUND: The CD163 is a marker of monocyte/macrophage anti-inflammatory function. Its soluble form (sCD163) also exert anti-inflammatory activities including inhibition of T cell proliferation. OBJECTIVE: To evaluate the effect of dexamethasone (Dx) and Dermatophagoides pteronyssinus (Dp) on ex vivo production of sCD163 by peripheral blood mononuclear cells (PBMCs). METHODS: PBMCs from 26 allergic asthma patients (AAs) and 12 non-atopic healthy controls (HCs) were cultured with Dp, Dx, Dp + Dx or without any stimulation for up to 144 h (T144). Concentration of sCD163, interleukin (IL) -6 and IL-10 in PMBC culture supernatants was evaluated using ELISA. The mRNA expression of CD163 by PBMCs was estimated using quantitative PCR (qPCR). RESULTS: At T144 the median concentration of CD163 in unstimulated PBMC cultures of AAs was greater than that in HCs (p = 0.008). Concomitant application of Dp and Dx resulted in a synergistic effect reflected by a dramatic increase of sCD163 concentration both in HCs (p = 0.0002) and AAs (p < 0.0001). Also a synergistic effect of Dp and Dx on CD163 mRNA expression was seen at T24 and T48 but not at T6 or T12. Among asthmatic patients the effect of Dx on sCD163 production was attenuated in severe in comparison to mild-to-moderate AAs (p = 0.0007). Moreover, Dp-induced production of IL-6 but not IL-10 was inhibited by Dx (p < 0.0001). Inhibition of IL-10 decreased sCD163 concentration by more than 50%. CONCLUSIONS: Dx-triggered upregulation of anti-inflammatory CD163 expression by monocytes is synergistic with endogenous mechanisms involved in the resolution of Dp-induced inflammation. This effect is impaired in severe asthma patients.


Assuntos
Alérgenos/imunologia , Antígenos CD/metabolismo , Antígenos de Dermatophagoides/imunologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Dermatophagoides pteronyssinus/imunologia , Dexametasona/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Receptores de Superfície Celular/metabolismo , Adulto , Animais , Anti-Inflamatórios/farmacologia , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Asma/diagnóstico , Asma/etiologia , Asma/metabolismo , Biomarcadores , Citocinas/genética , Citocinas/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/genética , Testes de Função Respiratória , Adulto Jovem
11.
Mayo Clin Proc ; 94(4): 652-659, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947832

RESUMO

The aim of this study was to characterize endothelial progenitor cells with osteoblastic phenotype (EPC-OCNs) and their role in individuals with varying degrees of aortic stenosis (AS). Peripheral blood mononuclear cells retrieved from blood samples of individuals with mild (n=40), moderate (n=35), or severe (n=103) AS from September 16, 2008, through March 30, 2015, were analyzed by flow cytometry for the EPC surface markers CD34, CD133, and kinase insert domain receptor (KDR) and the osteoblastic cell surface marker OCN. Levels of EPC-OCNs were correlated with AS severity and calcifications. Patients with severe AS had significantly elevated numbers of total circulating EPC-OCNs, including the EPC-OCN subtypes CD133+/OCN+, CD34+/CD133+/OCN+, and CD133+/KDR+/OCN+, compared with those with mild AS. Individuals with moderate AS also had significantly increased numbers of the circulating progenitor cell CD133+/OCN+ compared with patients with mild AS. There was a significant association between total circulating EPC-OCN levels and aortic valve (AV) calcification, AV mean gradient, and AV area measured by echocardiography. In summary, this study found the presence of circulating EPC-OCNs in patients with progressive AV stenosis. These findings might support the potential role for EPC-OCNs in the progression of AV stenosis and calcification.


Assuntos
Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico , Osteoblastos/fisiologia , Células-Tronco/fisiologia , Adulto , Idoso , Biomarcadores/sangue , Circulação Sanguínea/fisiologia , Calcinose/sangue , Calcinose/diagnóstico , Feminino , Humanos , Leucócitos Mononucleares/fisiologia , Masculino , Pessoa de Meia-Idade , Osteogênese/fisiologia
12.
BMC Psychiatry ; 19(1): 113, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987620

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a heritable, refractory, and devastating psychiatric disorder. Previous studies have shown that the variants of CUB and sushi multiple domains 1 (CSMD1) demonstrate significant genome-wide association with SCZ. However, few studies have been conducted on the effect of antipsychotics on the expression levels of CSMD1. This study explored whether a change occurs in the expression of the CSMD1 gene before and after antipsychotic treatment in SCZ patients. METHODS: The study population comprised Han Chinese patients from eastern China, including 32 SCZ patients and 48 healthy controls. The expression of CSMD1 before and after treatment in the SCZ group and between the two groups was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expression levels of the CSMD1 gene in the peripheral blood mononuclear cells (PBMCs) of SCZ patients were lower than those in the healthy controls. The expression levels of the CSMD1 gene in the PBMCs of the SCZ patients after antipsychotic treatment were higher than those in the baseline SCZ patients (all P <  0.05). CONCLUSIONS: Our results showed that the expression levels of CSMD1 are correlated with the development and treatment of SCZ, providing further evidence for the involvement of CSMD1 in SCZ.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença/genética , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Esquizofrenia/sangue , Esquizofrenia/genética , Proteínas Supressoras de Tumor/sangue , Proteínas Supressoras de Tumor/genética , Adulto , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Biomarcadores/sangue , China/epidemiologia , Feminino , Expressão Gênica , Predisposição Genética para Doença/epidemiologia , Estudo de Associação Genômica Ampla/métodos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esquizofrenia/tratamento farmacológico
13.
Immunol Invest ; 48(6): 618-631, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30961396

RESUMO

The pathophysiology of type 2 diabetes (T2DM) is associated with perturbation of innate immune response. Several studies indicated alteration of pro-inflammatory and anti-inflammatory cytokines, chemokines and other mediators of innate immune response in T2DM. This study was designed to perform quantitative PCR-based expression profiling of genes involved in inflammation (i.e. CASP1, CASP5, CCL5, CXC11, CCR5, NF-Κb, IL-4, PPARG and PGC1α) in peripheral blood leukocytes of T2DM patients. The T2DM patients are often prescribed with metformin and insulin while metformin has also been reported to possess anti-inflammatory activity. To address the question whether metformin exerts any effect on inflammatory mediators in bloodstream, human subjects in this study were divided into four groups on the basis of medication they were taking during last 6 month. These groups included NT-T2DM (T2DM patients not taking medication, n = 34), Met-T2DM (T2DM patients taking metformin, n = 33), INS-T2DM (T2DM patients taking insulin, n = 15) and NGT (normoglycemic subjects, n = 34) groups. Differential expression of gene transcripts at a cutoff of fourfold was considered significant. In the NT-T2DM group, transcripts of inflammation-related genes (i.e. CASP1, CASP5, CCL5, CCR5 and NF-kB) were up-regulated while transcripts of PPARG and PGC1α genes were down-regulated compared to NGT group. On the other hand, down-regulation of CASP1, CASP5, CCL5, CCR5 and NF-kB transcripts was evident in Met-T2DM and INS-T2DM groups when compared to the NT-T2DM group. The Met-T2DM group and INS-T2DM group showed a significant difference in the transcript level of CASP1 and CCL5 which are more down-regulated in the Met-T2DM group compared to INS-T2DM group. These findings indicated that (a) in T2DM, expression of inflammation-related genes is up-regulated and (b) anti-inflammatory activity of metformin appears to be independent of its anti-hyperglycemic activity.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Inflamação/genética , Leucócitos Mononucleares/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Caspase 1/genética , Quimiocina CCL5/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Insulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , NF-kappa B/genética
14.
Mol Nutr Food Res ; 63(8): e1800811, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30892810

RESUMO

SCOPE: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome. METHODS AND RESULTS: Older men (n = 31; 74.1 ± 0.6 y) are randomized to consume either RDA (0.8 g kg-1  day-1 ) or 2RDA (1.6 g kg-1  day-1 ) of protein for 10 weeks. Downregulation of five microRNAs (miR-125b-5p, -100-5p, -99a-5p, -23b-3p, and -203a) is observed following 2RDA with no changes in the RDA. In silico functional analysis highlights target gene enrichment in inflammation-related pathways. qPCR quantification of predicted inflammatory genes (TNFα, IL-8, IL-6, pTEN, PPP1CB, and HOXA1) in peripheral blood mononuclear cells shows increased expression following 2RDA diet (p ≤ 0.05). CONCLUSION: The study findings suggest a possible selective alteration in the post-transcriptional regulation of the immune system following a high protein diet. However, very few microRNAs are altered despite a large change in the dietary protein.


Assuntos
Ácidos Nucleicos Livres/sangue , Proteínas na Dieta/farmacologia , MicroRNAs/sangue , Idoso , Proteínas na Dieta/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Masculino , RNA Mensageiro , Recomendações Nutricionais
15.
Toxicol Lett ; 305: 110-116, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30708112

RESUMO

Fumonisin B1 (FB1), mainly produced by Fusarium verticillioides and Fusarium proliferatum, can be converted to the less toxic metabolite hydrolyzed FB1 (HFB1) by enzymatic degradation. The application of an FB1degrading enzyme as a feed additive is a strategy to reduce fumonisin exposure of animals. However, the difference between the effect of FB1 and HFB1 on porcine intestinal immunity is poorly documented. We investigated the toxic effects of FB1 and HFB1 exposure on porcine gut barrier function and intestinal immunity by using a co-culture model of intestinal porcine epithelial cells (IPEC-J2) and porcine peripheral blood mononuclear cells (PBMCs). First, we confirmed that Fusarium mycotoxin (deoxynivalenol; DON), in the presence of an endotoxin (lipopolysaccharide: LPS), disrupted gut permeability of IPEC-J2 and induced inflammatory response in the co-culture system. FB1 induced additional damage to gut barrier function and promoted pro-inflammatory responses in the presence of LPS and DON compared to only LPS/DON treatment. In the co-culture system, FB1/LPS/DON induced increased cell death of PBMCs and pro-inflammatory cytokines than LPS/DON treatment. In contrast, the application of HFB1 resulted in reduced levels of chemokines and pro-inflammatory cytokines together with marginal immune cell death compared to FB1/LPS/DON in the IPEC-J2/PBMC co-culture system. These findings suggest that FB1 aggravates LPS/DON-induced intestinal inflammation, and HFB1 showed less toxicity to immune response. Therefore, enzymatic degradation of FB1 to HFB1 could be an effective strategy to reduce intestinal inflammation in pigs.


Assuntos
Células Epiteliais/efeitos dos fármacos , Fumonisinas/química , Fumonisinas/toxicidade , Mucosa Intestinal/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Animais , Linhagem Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Técnicas de Cocultura , Células Epiteliais/fisiologia , Leucócitos Mononucleares/fisiologia , Suínos
16.
Mol Nutr Food Res ; 63(7): e1800990, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30702198

RESUMO

SCOPE: Some studies suggest that a high dietary intake of omega-6 fatty acids is pro-inflammatory. However, whether omega-6 fatty acids actually cause pathogenic inflammation in humans is debated. Therefore, the associations between expression of immunology-related genes in peripheral blood mononuclear cells (PBMCs) and serum total omega-6 PUFA status are investigated. METHODS AND RESULTS: Serum fatty acid profile and expression of 460 immunology-related genes in PBMCs from 58 healthy children (6-13 years) is measured, and examined the expression differences between children with high or low total omega-6 PUFA status (upper vs lower tertile). Taken together, both univariate analyses and integrated omics analyses support that while high omega-6 PUFA level associated with higher expressing of genes related to innate immune responses, it also associated with lower expression of several genes related to adaptive immune responses. CONCLUSION: Omega-6 PUFA status associated both positively and negatively with expression of specific immunology-related genes in PBMCs in healthy children. The results may suggest a nuanced role for omega-6 fatty acids in the interphase of lipids and inflammation, and warrants further examination in gene-environment studies and randomized controlled trials.


Assuntos
Imunidade Adaptativa/genética , Ácidos Graxos Ômega-6/sangue , Expressão Gênica , Imunidade Inata/genética , Leucócitos Mononucleares/fisiologia , Adolescente , Criança , Estudos Transversais , Ácidos Graxos Ômega-6/genética , Feminino , Expressão Gênica/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Masculino
18.
Parasitol Res ; 118(4): 1239-1248, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30788574

RESUMO

Haemonchus contortus is a highly pathogenic gastrointestinal nematode of small ruminant animals. In modern intensive farming, livestock often suffer from different types of stress. However, whether host stress hormones influence H. contortus infection is largely unknown. Therefore, we treated H. contortus with norepinephrine (NE) and analyzed the changes in its excretory/secretory products (ESPs). Label-free quantitative proteomic analysis was used to identify differences in body proteins and ESPs between the control and NE-treated groups. We also investigated the changes in ESP action by analyzing cytokine secretion and goat peripheral blood mononuclear cell (PBMC) proliferation after incubation with ESPs secreted by NE-treated H. contortus. Thirty-two proteins in the body samples and 137 in the ESPs were differentially expressed between the groups. Gene ontology (GO) annotation showed that the functions of these different proteins might be involved in energy metabolism, protein metabolism, lipid metabolism, redox homeostasis, ion channel, and cell structure. NE treatment caused oxidative stress in H. contortus and changed the expression levels of some immunogenic proteins, such as the 15-kDa ESP. Meanwhile, the ESPs secreted by NE-treated H. contortus significantly decreased PBMC proliferation and the interleukin (IL)-2, IL-4, and interferon-gamma contents. Thus, NE treatment significantly affected the H. contortus body and ESP expression, and changes in the ESPs influenced PBMC function. The results reveal a relationship between host hormones and parasites and provide new clues to explain some of the variation in individual responses to infection.


Assuntos
Gastroenteropatias/veterinária , Cabras/parasitologia , Hemoncose/veterinária , Haemonchus/efeitos dos fármacos , Haemonchus/metabolismo , Leucócitos Mononucleares/fisiologia , Norepinefrina/farmacologia , Proteínas de Protozoários/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Gastroenteropatias/parasitologia , Cabras/sangue , Hemoncose/parasitologia , Interferon gama/sangue , Interleucina-2/sangue , Interleucina-4/sangue , Estresse Oxidativo/efeitos dos fármacos , Ligação Proteica , Proteômica
19.
Hum Immunol ; 80(4): 257-262, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790598

RESUMO

INTRODUCTION: Chromosomal abnormalities are frequent events in hematological malignancies. The degree of HLA compatibility between donor and recipient in hematopoietic stem cell transplantation is critical. PURPOSE OF THE STUDY: In this report, we describe an acute myeloid leukemia case with loss of heterozygosity (LOH) encompassing the entire HLA. MATERIALS AND METHODS: HLA molecular typing was performed on peripheral blood (PB) and buccal swabs (BS). Chromosomal microarray analysis (CMA) was performed using a whole genome platform. RESULTS: Typing results on PB sample collected during blast crisis demonstrated homozygosity at the -A, -B, -C, -DR, and -DQ loci. A BS sample demonstrated heterozygosity at all loci. A subsequent PB sample drawn after count recovery confirmed heterozygosity. The CMA performed on PB samples collected during and after blast crisis revealed a large terminal region of copy-neutral LOH involving chromosome region 6p25.3p21.31, spanning approximately 35.9 Mb. The results of the CMA assay on sample collected after count recovery did not demonstrate LOH. CONCLUSIONS: LOH at the HLA gene locus may significantly influence the donor search resulting in mistakenly choosing homozygous donors. We recommend confirming the HLA typing of recipients with hematological malignancies when homozygosity is detected at any locus by using BS samples, or alternatively from PB when remission is achieved.


Assuntos
Medula Óssea/fisiologia , Genoma/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/genética , Leucócitos Mononucleares/fisiologia , Perda de Heterozigosidade , Complexo Principal de Histocompatibilidade/genética , Idoso , Circulação Sanguínea , Feminino , Teste de Histocompatibilidade , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Análise em Microsséries , Técnicas de Diagnóstico Molecular , Indução de Remissão
20.
Allergol Immunopathol (Madr) ; 47(4): 378-385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30745246

RESUMO

INTRODUCTION AND OBJECTIVES: Allergic asthma is a chronic inflammatory disorder of the airways. Th1, Th2 and Th17 cells are the main cells involved in the pathophysiology of asthma. The function of these cells is affected by T-bet, GATA3 and RORγt transcription factors (respectively). Therefore, the aim of this study was to evaluate the effect of ginger (officinal Roscoe) extract on the expression of T-bet, GATA-3 and ROR-γ in peripheral blood mononuclear cells (PBMC) of asthmatic patients, in comparison with healthy volunteers as controls. MATERIALS AND METHODS: In this case-control study, a total of 50 individuals including 25 patients with severe, moderate and mild allergic asthma and 25 unrelated healthy controls were involved. The PBMCs were isolated and divided into four groups: negative control, two positive controls (Budesonide and PHA) and ginger-extract treated group. After cell treatment and incubation for 48h, PBMCs were isolated and cDNA was synthesized. Gene expressions of T-bet, GATA3 and ROR-γt were evaluated by Real-time PCR. RESULTS: According to the results of this study, hydroalcoholic extract of ginger could reduce the expression of GATA-3, ROR-γt, and T-bet in PBMCs of asthmatic patients in comparison with untreated PBMCs (P values=0.001, 0.001, and 0.002, respectively). It was also shown that the ginger extract could affect T-bet/GATA-3, T-bet/ROR-γt, and ROR-γt/GATA-3 expression ratios. CONCLUSIONS: This study showed that the use of ginger extract could control asthma and decrease the severity of this disease by affecting the main cells involving the symptoms of asthma in the airways.


Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Fator de Transcrição GATA3/metabolismo , Hipersensibilidade/tratamento farmacológico , Leucócitos Mononucleares/fisiologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Extratos Vegetais/farmacologia , Proteínas com Domínio T/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Células Cultivadas , Criança , Fator de Transcrição GATA3/genética , Regulação da Expressão Gênica , Gengibre/imunologia , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Proteínas com Domínio T/genética , Adulto Jovem
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