RESUMEN
BACKGROUND: Cystic fibrosis (CF) is a genetic multisystem disorder. Inflammatory processes, which presumably begin early in infancy, play a crucial role in the progression of the disease. The detection of inflammatory biomarkers, especially in the airways, has therefore gained increasing attention. Due to improved treatment options, patients with CF produce less sputum. Nasal lavage samples therefore represent a promising alternative to induced sputum or bronchoalveolar lavage specimens. However, methodology of cytokine measurements is not standardised and comparisons of results are therefore often difficult. The aim of this study was to identify suitable detection methods of cytokines in nasal lavage samples by comparison of two different assays. METHODS: Nasal lavage samples were obtained from the same patient at the same time by trained respiratory physiotherapists using a disposable syringe and 10 ml of 0.9% sodium chloride per nostril during outpatient visits. The cytokines IL-17 A, IL-2, IL-6 and IL-10 were measured using two different assays (BD™ and Milliplex®), which have already been applied in sputum and nasal lavage samples, despite different lower detection limits. RESULTS: 22 participants were included in the study. In 95.5% of measurements, values were below the limit of detection with respect to the BD™ assay. Only IL-6 could be detected in approximately half of the patients. Individual cytokine levels were considerably higher when measured with Milliplex®, which is also reflected in a statistically significant manner (p = < 0.01). CONCLUSION: The right choice of analysis method is crucial for measuring inflammatory markers in nasal lavage samples. Compared to the literature, Milliplex® showed higher detection rates and similar concentrations to other studies. TRIAL REGISTRATION: Ethics approval was obtained from the ethics committee at Medical University of Innsbruck (EK Nr: 1055/2022).
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Fibrosis Quística , Citocinas , Líquido del Lavado Nasal , Humanos , Fibrosis Quística/diagnóstico , Masculino , Femenino , Citocinas/análisis , Citocinas/metabolismo , Adulto , Adolescente , Líquido del Lavado Nasal/química , Adulto Joven , Biomarcadores/análisis , Biomarcadores/metabolismo , Niño , Interleucina-6/análisis , Interleucina-6/metabolismo , Interleucina-10/análisis , Interleucina-10/metabolismo , Interleucina-2/análisis , Interleucina-2/metabolismo , Interleucina-17/análisis , Interleucina-17/metabolismoRESUMEN
During bovine mastitis, immune responses include the release of cytokines and the recruitment of leukocytes, resulting in profound structural and functional changes in the mammary gland. Our aims were to delineate systemic and local cytokine responses and to quantify histological changes in the mammary tissue of lactating cows after acute intramammary lipopolysaccharide (LPS) challenge. Ten multiparous dairy cows were paired to either treatment (TRT) or control (CON) groups. For TRT cows, one side of the udder was randomly assigned to receive treatment with LPS (50 µg in 10 mL of saline, TL) into both the front and rear quarters; the contralateral quarters received saline (10 mL). Udder-halves of CON cows were similarly assigned randomly to receive either saline (10 mL, CS) or no infusion (untreated). Temporal changes in the concentrations of 15 cytokines in the blood (0, 3, 6, 12, and 24 h relative to the LPS infusion) and in mammary tissue (0, 3, and 12 h) were determined, as were concomitant changes in mammary histology. The cytokines IL-6, IL-10, MCP-1, and MIP-1ß showed a systemic response as their concentrations were significantly different in the plasma of TRT cows as compared with CON cows after LPS challenge. The cytokines IL-1α, IL-1ß, IL-6, IL-8, IL-17A, IL-36RA, IP-10, MCP-1, MIP-1α, MIP-1ß, TNF-α, and VEGF-A showed a local response in TL glands, and 8 cytokines, IL-1ß, IL-6, IL-10, IL-17A, IL-36RA, IP-10, MIP-1ß, and VEGF-A showed systemic changes in the nonchallenged mammary glands adjacent to LPS-infused glands. Endotoxin challenge evoked changes in the histology of mammary tissue that included a 5.2- and 7.2-fold increases in the number of neutrophils in alveolar lumens at 3 h and 12 h, respectively. In summary, LPS challenge induced specific local and systemic responses in cytokine induction and elicited neutrophil infiltration in bovine mammary tissue.
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Enfermedades de los Bovinos , Mastitis Bovina , Femenino , Bovinos , Animales , Citocinas/análisis , Lipopolisacáridos/farmacología , Lipopolisacáridos/análisis , Lactancia , Interleucina-10 , Leche/química , Interleucina-17/análisis , Quimiocina CCL4/análisis , Quimiocina CXCL10/análisis , Interleucina-6 , Factor A de Crecimiento Endotelial Vascular , Glándulas Mamarias AnimalesRESUMEN
Abstract The aim of this study was to evaluate tumor necrosis factor alpha (TNF-α), interleukin (IL)- 17A/F levels in the serum of ankylosing spondylitis (AS) patients after anti-TNF therapy, in order to understand how these cytokines are involved in this therapeutic response. Forty-four AS patients were included in the study: thirty using anti-TNF therapy were classified according to their therapy response as responders (15) and non-responders (15) and 14 without anti-TNF therapy were classified as AS control. Fifteen healthy individuals formed the control group. Serum levels of TNF-α were determined using Luminex technology and for IL-17A and IL-17F using ELISA. The non-responder patients presented higher serum levels of TNF-α than the responders and AS control; the same results were found when HLA-B*27 positive or negative patients were separately analyzed. IL-17A and IL17F serum levels were similar for all groups. According to the clinical disease activity, AS patients with BASDAI ≥4 had higher serum levels of TNF-α than AS patients with BASDAI <4. Positive correlation was found between TNF-α levels and BASDAI. In AS patients, TNF-α serum levels were associated with anti-TNF therapy and disease activity independently of HLA-B*27, and IL-17A and IL-17F were not related to anti-TNF treatment
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Humanos , Masculino , Femenino , Pacientes/clasificación , Espondilitis Anquilosante/patología , Factor de Necrosis Tumoral alfa/análisis , Interleucina-17/análisis , Polimorfismo Genético , Citocinas/clasificación , Estudios de Asociación Genética/instrumentaciónRESUMEN
PURPOSE: To investigate the relationship between polymorphism of cytochrome P450, family 2, subfamily A, polypeptide 6(CYP2A6) and periodontitis, the expression of inflammatory cytokines in 123 Han smokers. METHODS: From October 2018 to October 2019, a total of 123 smokers with periodontitis were selected as the experimental group, and 125 non-smokers as the control group. The general data of the patients were collected, including age, gender, body mass index (BMI), chewing and brushing habits, as well as molar condition; plaque index (PLI), gingival bleeding index (BI), periodontal probing depth (PD) and attachment loss (AL) were detected. CYP2A6 was amplified by PCR. The level of interleukin (IL)-17, IL-1, IL-6, IL-23 and tumor necrosis factor-α (TNF-α) in GCF was detected by enzyme-linked immunosorbent assay(ELISA). SPSS 25.0 software package was used for statistical analysis of the data. RESULTS: There was significant difference in gender, PLI, IL-17, IL-1, IL-6, IL-23, TNF-α level in GCF between the two groups(Pï¼0.05). All samples were amplified by PCR. Among them, 23 were not amplified, which were identified as CYP2A6 deletion type (CYP2A6del), including 5 in the experimental group and 18 in the control group; 225 were amplified and identified as CYP2A6 wild type(CYP2A6wt), including 118 in the experimental group and 107 in the control group. There was significant difference in CYP2A6 genotype between the two groups(Pï¼0.05). In the experimental group, the level of IL-1 and PLI of different CYP2A6 genotypes was significantly different(Pï¼0.05); and in the control group, the level of IL-17 and PLI of different CYP2A6 genotypes was also significantly different(Pï¼0.05). CONCLUSIONS: There are differences in CYP2A6 genotype between smokers and non-smokers in Han population with periodontitis, but the relationship between CYP2A6 genotype and inflammatory cytokines is not clear.
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Líquido del Surco Gingival , Periodontitis , Niño , Citocromo P-450 CYP2A6 , Citocinas , Susceptibilidad a Caries Dentarias , Humanos , Interleucina-1/análisis , Interleucina-1/genética , Interleucina-17/análisis , Interleucina-23/análisis , Interleucina-6 , Periodontitis/genética , Diente Primario , Factor de Necrosis Tumoral alfaRESUMEN
Background and Objectives: The elicitation of a host's immune−inflammatory responses to overcome oral bacterial biofilm challenges is mediated by numerous cytokines. We explored the role of three such cytokines, viz. interleukin (IL)-17, 18 and 21, by measuring their levels in the gingival crevicular fluid (GCF) of Indian individuals with healthy gingiva, chronic gingivitis, or chronic periodontitis. Materials and Method: Ninety systemically healthy individuals were enrolled in the study on the basis of predefined criteria and were categorized into three groups of 30 participants each. Groups A, B and C were composed of a control group with healthy gingiva, subjects with chronic gingivitis and subjects with chronic periodontitis, respectively. The periodontal disease status was assessed on the basis of a subject's gingival index, probing pocket depth, clinical attachment loss and radiographic evidence of bone loss. After the complete history-taking and identification of gingival sulcus/pocket depth areas for GCF collection, a sample was collected from each subject in all groups for an estimation of the cytokine levels using ELISA. Statistical analysis was performed using SPSS v 21.0. Intergroup comparisons were conducted using a post hoc Tukey's test. A value of p < 0.05 was considered to be statistically significant. Results: The mean IL-17, 18 and 21 concentrations in pg/mL was the greatest for Group C (99.67 ± 18.85, 144.61 ± 20.83 and 69.67 ± 12.46, respectively), followed by Group B (19.27 ± 2.78, 22.27 ± 2.43 and 22.74 ± 1.43, respectively) and finally by Group A (healthy control; 11.56 ± 0.99, 17.94 ± 1.24 and 12.83 ± 1.21 respectively). A statistically significant difference in the mean concentrations of two interleukins (IL-17 and IL-18) was observed between Groups A and C and also between Groups B and C. A statistically significant difference in the mean concentrations of IL-21 was observed between Groups B and C. Conclusions: Within the limitations of the present study, the findings revealed that the GCF levels of IL-17, IL-18 and IL-21 rose and correlated well with the severity of the disease. Thus, these cytokines present in GCF have the potential to be considered as biomarkers for periodontal tissue destruction. IL-21 in particular appears to be a promising biomarker for differentiating between gingivitis and periodontitis.
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Periodontitis Crónica , Gingivitis , Biomarcadores/análisis , Citocinas/análisis , Líquido del Surco Gingival/química , Humanos , Interleucina-17/análisis , Interleucina-18 , Pérdida de la Inserción PeriodontalRESUMEN
OBJECTIVE: Periodontitis in younger patients can cause severe periodontal destruction, and cases are usually more numerous in members of the same family due to the sharing of susceptibility factors. Thus, the use of a familial study design could improve our understanding of initial alterations in periodontal tissue. This observational study aimed to evaluate the salivary inflammatory pattern in descendants of periodontitis patients and identify any correlation with the clinical periodontal condition. STUDY DESIGN: Fifteen children of Generalized Aggressive Periodontitis (GAgP) patients and 15 children with periodontally healthy parents were evaluated for their plaque index (PI), gingival index (GI), bleeding on probing (BoP), and probing depth (PD). The concentrations of interferon (IFN)-γ, interleukin (IL)-10, IL-17, IL-1ß, IL-4, and tumor necrosis factor (TNF)-α were measured in unstimulated saliva using the Luminex MAGPix platform. RESULTS: Children from the GAgP group presented higher probing depth (PD) and bleeding on probing (BoP) (p<0.05) and lower release of IL-4 in saliva (p<0.05) than the periodontally healthy group. The cytokines IL-10, IFN-γ, IL-17, and IL-4 were negatively correlated with the gingival index, while IL-4 was negatively correlated with BoP. A regression analysis revealed that salivary IL-4 and plaque were predictors of BoP. CONCLUSIONS: Children of GAgP parents presented lower salivary IL-4 and higher BoP and PD than children from periodontally healthy families. Additionally, salivary IL-4 was a predictor of bleeding on probing in the children, suggesting that the lower presence of this anti-inflammatory cytokine is related to higher clinical inflammation.
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Periodontitis Agresiva , Interleucina-17 , Niño , Citocinas , Índice de Placa Dental , Humanos , Interleucina-17/análisis , Interleucina-4 , Índice Periodontal , Saliva/química , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoimmunity. No objective clinical indicators are available for the diagnosis and prognosis of MS. Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers. Our work will contribute to the in-depth study of the functions of extracellular proteins and the discovery of disease biomarkers. Methods: MS expression profiling data of the human brain was downloaded from the Gene Expression Omnibus (GEO). Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases. GO and KEGG were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the CSF of MS patients. ROC curve and survival analysis were used to evaluate the diagnostic and prognostic ability of key EP-DEGs. Results: We screened 133 EP-DEGs from DEGs. EP-DEGs were enriched in the collagen-containing extracellular matrix, signaling receptor activator activity, immune-related pathways, and PI3K-Akt signaling pathway. The PPI network of EP-DEGs had 85 nodes and 185 edges. We identified 4 key extracellular proteins IL17A, IL2, CD44, IGF1, and 16 extracellular proteins that interacted with IL17A. We clinically verified that IL17A levels decreased, but Del-1 and resolvinD1 levels increased. The diagnostic accuracy of Del-1 (AUC: 0.947) was superior to that of IgG (AUC: 0.740) with a sensitivity of 82.4% and a specificity of 100%. High Del-1 levels were significantly associated with better relapse-free and progression-free survival. Conclusion: IL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS. We used bioinformatics methods to explore the biomarkers of MS and validated the results in clinical samples. The study provides a theoretical and experimental basis for revealing the pathogenesis of MS and improving the diagnosis and prognosis of MS.
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Líquido Extracelular/química , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Proteínas/análisis , Adulto , Biomarcadores , Química Encefálica , Proteínas de Unión al Calcio/análisis , Proteínas de Unión al Calcio/fisiología , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/fisiología , Proteínas del Líquido Cefalorraquídeo/análisis , Proteínas del Líquido Cefalorraquídeo/genética , Conjuntos de Datos como Asunto , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Cefalea/genética , Cefalea/metabolismo , Humanos , Interleucina-17/análisis , Interleucina-17/fisiología , Masculino , Persona de Mediana Edad , Anotación de Secuencia Molecular , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/genética , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Supervivencia sin Progresión , Análisis por Matrices de Proteínas , Mapas de Interacción de Proteínas , Proteínas/genética , Sensibilidad y EspecificidadRESUMEN
Human regulatory T (Treg) cells play a central role in controlling allergic inflammation in the airways. A reduced number of peripheral Treg cells and decreased suppressive function have been previously reported in the pathogenesis of allergic asthma. However, the characteristic role of specific Treg cell subsets and their mechanisms in the pathogenesis of allergic asthma remain unclear. In this study, we examined the proportion of different Treg cell subsets in both healthy subjects and patients with allergic asthma using flow cytometry and single-cell RNA sequencing. The migration function of the cells was compared using cell sorting and Transwell experiments. Furthermore, two allergen-challenged mouse models and a cell transfer experiment were used to examine the role of these Treg subsets. We found that the proportion of CD25+Foxp3+CD127- Treg cells in the peripheral blood of patients with allergic asthma was lower than in those of healthy subjects. Furthermore, the circulating Treg cells expressed lower levels of CCR6 and IL-17 compared with healthy subjects. The chemokine from the airway mucosa, CCL20, was abundantly expressed, and Transwell experiments further proved that this chemokine promoted CCR6+ Treg cell migration in vitro. A mouse model induced by house dust mite (HDM) revealed that the number of CCR6+ Treg cells in the lung tissue increased remarkably. The incidence of allergic asthma may be related to an increase in Treg cells secreting IL-17 in the lung tissue. Recruited CCR6+ Treg cells are likely to differentiate into Th17-like cells under the Th17 environment present in the lungs. IL-17 derived from Th17-like cells could be associated with the pathology of allergic asthma by promoting Th17 responses, thereby favoring HDM-induced asthma exacerbations.
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Asma/inmunología , Hipersensibilidad/inmunología , Interleucina-17/análisis , Pulmón/inmunología , Receptores CCR6/fisiología , Linfocitos T Reguladores/inmunología , Adulto , Animales , Antígenos CD4/análisis , Femenino , Humanos , Subunidad alfa del Receptor de Interleucina-2/análisis , Masculino , Ratones , Ratones Endogámicos C57BL , Pyroglyphidae , Receptores CCR6/análisisRESUMEN
This study aimed to evaluate the clinical evolution, functional parameters and inflammatory activity of asthma in patients who submitted to an educational intervention. 58 adult patients over 18 years of age with partly controlled and uncontrolled asthma were randomized into an intervention group (IG) (N = 32) and a control group (CG) (N = 26) and evaluated for 12 weeks. The Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Asthma Quality Life Questionnaire (AQLQ) and Beck Depression Inventory (BDI) questionnaires were applied. Spirometry, exhaled nitric oxide (NO), exhaled breath condensate (EBC) and induced sputum (IS), measurement of the peak flow and symptoms were performed. The IG patients received an educational activity for 30 min applied by a nurse. Statistical analysis: analysis of variance with repeated intragroup measures. IG presented a decreased number of eosinophils in IS and IL-17A in EBC, an increase in the percentage of FEV1 before and after bronchodilator and an improvement in quality of life compared to the CG. There was an improvement in depression levels and a decrease in IL-4 and IL-5 in the IS and in the EBC in both groups. Our results suggest that an educational intervention can bring benefits concerning the control of inflammation, lung function alterations, quality of life and levels of depression in asthmatic patients. Registration: ClinicalTrials.gov; NCT03655392.
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Asma/terapia , Inflamación/prevención & control , Educación del Paciente como Asunto , Pruebas Respiratorias , Femenino , Volumen Espiratorio Forzado , Humanos , Interleucina-17/análisis , Interleucina-4/análisis , Interleucina-5/análisis , Masculino , Persona de Mediana Edad , Óxido Nítrico/análisis , Educación del Paciente como Asunto/métodos , Calidad de Vida , Espirometría , Esputo/química , Encuestas y CuestionariosRESUMEN
PURPOSE: IL-17 is an important effector cytokine driving immune-mediated destruction in autoimmune diseases such as psoriasis. Blockade of the IL-17 pathway after the initiation of insulitis was effective in delaying or preventing the onset of type 1 diabetes (T1D) in rodent models. Expression of IL-17 transcripts in islets from a donor with recent-onset T1D has been reported, however, studies regarding IL-17 protein expression are lacking. We aimed to study whether IL-17 is being expressed in the islets of diabetic donors. METHODS: We stained human pancreatic tissues from non-diabetic (n = 5), auto-antibody positive (aab+) (n = 5), T1D (n = 6) and T2D (n = 5) donors for IL-17, Insulin, and Glucagon, and for CD45 in selected cases. High resolution images were acquired with Zeiss laser scanning confocal microscope LSM780 and analyzed with Zen blue 2.3 software. Cases stained for CD45 were also acquired with widefield slide scanner and analyzed with QuPath software. RESULTS: We observed a clear cytoplasmic staining for IL-17 in insulin-containing islets of donors with T1D and T2D, accounting for an average of 7.8 ± 8.4% and 14.9 ± 16.8% of total islet area, respectively. Both beta and alpha cells were sources of IL-17, but CD45+ cells were not a major source of IL-17 in those donors. Expression of IL-17 was reduced in islets of non-diabetic donors, aab+ donors and in insulin-deficient islets of donors with T1D. CONCLUSION: Our finding that IL-17 is expressed in islets of donors with T1D or T2D is quite intriguing and warrants further mechanistic studies in human islets to understand the role of IL-17 in the context of metabolic and immune stress in beta cells.
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Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 2/inmunología , Células Secretoras de Glucagón/inmunología , Células Secretoras de Insulina/inmunología , Interleucina-17/análisis , Donantes de Tejidos , Adolescente , Adulto , Preescolar , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: An alarming increase in the number of patients with chronic and recurrent dermatophytosis has invoked the need to study the immunological parameters of the host. OBJECTIVES: To evaluate delayed type of hypersensitivity (DTH) response and immediate hypersensitivity (IH) response by flow cytometry evaluation of immune cells from peripheral blood and intradermal trichophyton skin test in patients with recurrent dermatophytosis. METHODS: A hundred patients with recurrent dermatophytosis and 50 controls (healthy controls and acute dermatophytosis controls) were included. Relevant risk factors for recurrence were analysed, and serum IgE levels were estimated. Flow cytometry evaluation of immune cells in peripheral blood and intradermal trichophyton skin test was done. Dermatophyte pathogens were isolated, and antifungal susceptibility was performed. RESULTS: Trichophyton mentagrophytes complex (95.84%) and T. rubrum (4.16%) were isolated in culture. Serum IgE was elevated in 83.15% cases (p = .01). IFN-γ+ cells (p = .0501, p = .0001, p = .0014), Th1 cells (p = .1197, p = .0024, p = .0169), IL-17+ cells (p = .0127, p = .0006, p = .0007) and Th17 cells (p = .0634, p = .0001, p = .0054) were reduced, and IL-4+ cells (p = .0108, p = .0175, p = .0018) were increased in cases. Intradermal test demonstrated negative DTH response in all cases (p < .001, p < .001, p < .001), strongly positive IH response in 6%, and borderline positive IH response in 85% cases (p = .018, p < .001, p < .001). Topical corticosteroids application, undergarment types (tight fit), poor frequency of washing clothes, family history of tinea, sharing of towels were significant risk factors for recurrent dermatophytosis. CONCLUSIONS: Reduced IFN-γ+ , Th1, IL-17+ and Th17 cells population along with impaired DTH response by the intradermal test was observed in patients with recurrent dermatophytosis.
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Tiña/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Hipersensibilidad Tardía , Inmunoglobulina E/sangre , India , Interferón gamma/análisis , Interleucina-17/análisis , Interleucina-4/análisis , Pruebas Intradérmicas , Masculino , Recurrencia , Sensibilidad y Especificidad , Centros de Atención Terciaria , Células TH1RESUMEN
Background: Helicobacter pylori infection is the main cause of chronic gastritis in children. Little is known about the effect of Helicobacter pylori on microbiota and immunity. This study was aimed at characterizing stomach microbiota and immune-regulatory properties of children with Helicobacter pylori colonization. Methods: We studied 122 children who had undergone gastric endoscopy due to gastrointestinal symptoms, 57 were diagnosed with Helicobacter pylori infection. Endoscopic mucosal biopsy samples were obtained for DNA and RNA extraction. Microbiomes were analyzed by 16S rRNA profiling, with the differentially expressed genes analyzed using RNA sequencing. The RNA-sequencing results of selected genes were validated by qRT-PCR. Results: Bacterial diversity of Helicobacter pylori-positive gastric specimens were lower than those of negative, and both groups were clearly separated according to beta diversity. Helicobacter pylori-positive group significantly reduced proportions of six phyla and eight genera; only Helicobacter taxa were more abundant in Helicobacter pylori-negative group. Gastric tissues RNA sequencing showed increased expression of multiple immune response genes in Helicobacter pylori -infection. Helicobacter pylori -infected children with restructured gastric microbiota had higher levels of FOXP3, IL-10, TGF-ß1 and IL-17A expressions, which were consistent with increased CD4+T cell and macrophagocyte, compared with non-infected children. Conclusions: Presence of Helicobacter pylori significantly influences gastric microbiota and results in lower abundance of multiple taxonomic levels in children. Meanwhile, it affects gastric immune environment and promotes the occurrence of gastritis. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1800015190].
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Duodeno/microbiología , Mucosa Gástrica/microbiología , Gastritis/microbiología , Microbioma Gastrointestinal , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Inmunidad Mucosa , Mucosa Intestinal/microbiología , Adolescente , Factores de Edad , Biopsia , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/microbiología , Estudios de Casos y Controles , Niño , Duodeno/inmunología , Disbiosis , Endoscopía Gastrointestinal , Femenino , Factores de Transcripción Forkhead/análisis , Mucosa Gástrica/inmunología , Gastritis/diagnóstico , Gastritis/inmunología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Interacciones Huésped-Patógeno , Humanos , Interleucina-10/análisis , Interleucina-17/análisis , Mucosa Intestinal/inmunología , Macrófagos/inmunología , Macrófagos/microbiología , Masculino , Ribotipificación , Factor de Crecimiento Transformador beta1/análisisRESUMEN
Obesity is associated with an impaired balance of CD4+ T cell subsets. Both vitamin D and obesity have been reported to affect the mTOR pathway. In this study, we investigated the effects of vitamin D on CD4+ T cell subsets and the mTOR pathway. Ten-week-old male C57BL/6 mice were divided into four groups and fed diets with different fat (control or high-fat diets: CON or HFD) and vitamin D contents (vitamin D control or supplemented diets: vDC or vDS) for 12 weeks. T cells purified by negative selection were stimulated with anti-CD3/anti-CD28 mAbs and cultured for 48 h. The percentage of CD4+IL-17+ T cells was higher in the vDS than vDC groups. The CD4+CD25+Foxp3+ T cells percentage was higher in HFD than CON groups. The phospho-p70S6K/total-p70S6K ratio was lower in vDS than vDC, but the phospho-AKT/total-AKT ratio was higher in vDS than vDC groups. Hif1α mRNA levels were lower in vDS than vDC groups. These findings suggest HIF1α plays an important role in vitamin-D-mediated regulation of glucose metabolism in T cells, and dietary vitamin D supplementation may contribute to the maintenance of immune homeostasis by regulating the mTOR pathway in T cells.
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Linfocitos T CD4-Positivos/efectos de los fármacos , Dieta Alta en Grasa , Obesidad/inmunología , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Vitamina D/administración & dosificación , Animales , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Suplementos Dietéticos , Factores de Transcripción Forkhead/análisis , Expresión Génica/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Interferón gamma/biosíntesis , Interleucina-17/análisis , Interleucina-4/biosíntesis , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/metabolismo , ARN Mensajero/análisis , Transducción de Señal/genética , Transducción de Señal/fisiología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Serina-Treonina Quinasas TOR/genética , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitamina D/metabolismoRESUMEN
OBJECTIVE: To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor myelin-specific T cells in their central nervous system (CNS) and periphery. METHODS: Mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs) and peripheral blood of Japanese macaques (JMs) with JME, and cervical LN and blood MNCs from healthy controls or animals with non-JME conditions were analyzed for the presence of myelin-specific T cells and changes in interleukin 17 (IL-17) and interferon gamma (IFNγ) expression. RESULTS: Demyelinating JME lesions contained CD4+ T cells and CD8+ T cells specific to myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and/or proteolipid protein (PLP). CD8+ T-cell responses were absent in JME peripheral blood, and in age- and sex-matched controls. However, CD4+ Th1 and Th17 responses were detected in JME peripheral blood versus controls. Cervical LN MNCs from eight of nine JME animals had CD3+ T cells specific for MOG, MBP, and PLP that were not detected in controls. Mapping myelin epitopes revealed a heterogeneity in responses among JME animals. Comparison of myelin antigen sequences with those of JM rhadinovirus (JMRV), which is found in JME lesions, identified six viral open reading frames (ORFs) with similarities to myelin antigen sequences. Overlapping peptides to these JMRV ORFs did not induce IFNγ responses. INTERPRETATIONS: JME possesses an immune-mediated component that involves both CD4+ and CD8+ T cells specific for myelin antigens. JME may shed new light on inflammatory demyelinating disease pathogenesis linked to gamma-herpesvirus infection.
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Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/patología , Encefalomielitis/diagnóstico por imagen , Encefalomielitis/patología , Vaina de Mielina/inmunología , Linfocitos T/inmunología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Desmielinizantes/virología , Encefalomielitis/virología , Ensayo de Inmunoadsorción Enzimática , Mapeo Epitopo , Epítopos/genética , Epítopos/inmunología , Femenino , Infecciones por Herpesviridae/inmunología , Interferón gamma/análisis , Interleucina-17/análisis , Macaca fuscata , Masculino , Enfermedades de los Monos , Proteína Básica de Mielina/genética , Proteína Básica de Mielina/inmunología , Proteína Proteolipídica de la Mielina/genética , Proteína Proteolipídica de la Mielina/inmunología , Vaina de Mielina/patología , Glicoproteína Mielina-Oligodendrócito/genética , Glicoproteína Mielina-Oligodendrócito/inmunología , Rhadinovirus/genética , Rhadinovirus/inmunologíaRESUMEN
Interleukin-17A (IL-17A) is a member of the Interleukin-17 family, which belongs to the pro-inflammatory cystine-knot cytokines. Recent studies on the etiology of breast cancer have focused on the role of immunity and inflammation. The pro-inflammatory cytokines IL-17A can medicate cancer-related inflammation. The present study aimed to analyze the mutation in physicochemical properties and structure of the Interleukin-17 A gene in developing breast cancer using bioinformatics methods. A total of 60 blood samples were obtained from Iraqi women aged 25 to 75 with breast cancer. Twenty blood samples were obtained from healthy women in the same age range as a control group. Deletion and missense mutations detected by BLAST in samples with breast cancer. The present study determined the physicochemical properties of IL-17A such as hydrophilic nature, alpha-helical and 3D structure. The results of this study indicated that IL-17A is considered a marker for a patient with breast cancer. Also, mutations in the IL-17A gene affect the structure and physicochemical properties of the IL-17A protein complex.
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Neoplasias de la Mama , Biología Computacional , Interleucina-17 , Neoplasias de la Mama/diagnóstico , Biología Computacional/métodos , Citocinas , Femenino , Humanos , Inflamación/metabolismo , Interleucina-17/análisisRESUMEN
Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalomyelitis (EAE) in mice, by focusing on HuR, an RNA-binding protein involved in inflammatory and immune phenomena. Spinal cord sections of EAE mice showed an increased HuR immunostaining that was abundantly detected in the cytoplasm of activated microglia, a pattern associated with its increased activity. Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) decreased the proinflammatory activated microglia, inflammatory infiltrates, and the expression of the proinflammatory cytokines IL-1ß, TNF-α, and IL-17, and inhibited the activation of the NF-κB pathway. The beneficial effect of anti-HuR ASO in EAE mice corresponded also to a decreased permeability of the blood-brain barrier. EAE mice showed a reduced spinal CD206 immunostaining that was restored by anti-HuR ASO, indicating that HuR silencing promotes a shift to the anti-inflammatory and regenerative microglia phenotype. Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss. Targeting HuR might represent an innovative and promising perspective to control neurological disturbances in MS patients.
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Proteína 1 Similar a ELAV/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , Animales , Western Blotting , Proteína 1 Similar a ELAV/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Interleucina-17/análisis , Interleucina-17/sangre , Interleucina-1beta/análisis , Interleucina-1beta/sangre , Ratones , Microglía/efectos de los fármacos , Microglía/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Oligonucleótidos Antisentido/farmacología , Prueba de Desempeño de Rotación con Aceleración Constante , Médula Espinal/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/sangreRESUMEN
ABSTRACT: Chagas disease affects approximately 7 million people, causing disability and mortality in the most productive life stages of infected individuals. Considering the lifestyle of the world population, metabolic syndrome is a synergistic factor for an increased cardiovascular risk of patients with Chagas disease.This study transversally evaluated the metabolic and immunological profiles of patients with indeterminate (IF) and cardiac (CF) forms of Chagas disease and their correlations with left ventricular dysfunction (LVD).Clinical and electrical bioimpedance analysis, levels of cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-17, IL-10, and IL-33) and adipocytokines (adiponectin, leptin, and resistin), metabolic syndrome components, and brain natriuretic peptide (BNP) levels were assessed in 57 patients (13 IF and 44 CF) with a mean age of 61.63â±â12.1 years. Chest x-ray, electrocardiogram, and echocardiogram were performed to classify the clinical forms.The CF group had a higher number of individuals with metabolic syndrome components blood pressure altered, while more participants in the CF group with LVD had low high-density lipoprotein (HDL) levels. The IF group had more participants with a higher waist-to-hip ratio (WHR). No significant difference was observed between metabolic syndrome, cytokine and adipocytokine level, and clinical forms of the disease or in relation to LVD.Individuals with the IF showed metabolic and immunological profiles compatible with increased disease control, whereas those with CF showed marked inflammatory immune response.
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Enfermedad de Chagas/inmunología , Enfermedad de Chagas/metabolismo , Adiponectina/análisis , Adiponectina/sangre , Anciano , Análisis de Varianza , Biomarcadores/análisis , Biomarcadores/sangre , Femenino , Cardiopatías/inmunología , Cardiopatías/metabolismo , Humanos , Interleucina-10/análisis , Interleucina-10/sangre , Interleucina-17/análisis , Interleucina-17/biosíntesis , Interleucina-33/análisis , Interleucina-33/sangre , Leptina/análisis , Leptina/sangre , Masculino , Persona de Mediana Edad , Resistina/análisis , Resistina/sangre , Estadísticas no ParamétricasRESUMEN
Since Marine sponge Dysidea avara is regarded as a source of anti-inflammatory compounds, we decided to evaluate its potential anti-psoriatic activity in a psoriasis Imiquimod-induced in the mouse model. Psoriatic mice were treated with three different methanolic extracts of Dysidea avara compared with betamethasone-treated mice in in- vivo studies. Clinical skin severity was assessed with the psoriasis area index (PASI), whilst ELISA detected the expression of TNF-α, IL-17A, and IL-22. Dysidea avara activity was studied by employing GC-MS (to distinguish compounds), HPTLC (for skin permeation and accumulation), and SEA DOCK to predict single compound potential anti-inflammatory activity. After 7 days of treatment, mice treated with Dysidea avara displayed a dose-dependent, statistically significant improvement compared to controls (p< 0.001). In line with the clinical results, ELISA revealed a statistically significant decrease in IL-22, IL-17A, and TNF-α after treatment; the same SEA DOCK analysis suggests a possible anti-psoriatic activity of the extracts.
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Antiinflamatorios/farmacología , Productos Biológicos/farmacología , Dysidea , Psoriasis/tratamiento farmacológico , Piel/efectos de los fármacos , Animales , Antiinflamatorios/uso terapéutico , Productos Biológicos/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Imiquimod/toxicidad , Interleucina-17/análisis , Interleucina-17/metabolismo , Interleucinas/análisis , Interleucinas/metabolismo , Ratones , Psoriasis/inducido químicamente , Psoriasis/diagnóstico , Psoriasis/inmunología , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/metabolismo , Piel/patología , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-22RESUMEN
In the United States, prevalence of marijuana-use has doubled in the past 2 decades. The aim was to compare the periodontal conditions and whole-salivary IL-17A and IL-23 levels among young adult marijuana-smokers, heavy cigarette-smokers and non-smokers. Self-reported marijuana-smokers, heavy-cigarette-smokers, non-smokers with periodontitis and periodontally-healthy non-smokers were included. Demographic data was recorded and full-mouth plaque index (PI), bleeding on probing (BoP), probing depth (PD) and clinical attachment loss (AL), marginal bone loss (MBL) and missing teeth were recorded. Levels of IL-17A and IL-23 levels were measured in the whole saliva. p < 0.01 was considered statistically significant. Fifteen-marijuana-smokers, 15 heavy-cigarette-smokers, 16 non-smokers-with-periodontitis and 15 periodontally-healthy-non-smokers) were included. The clinicoradiographic parameters were worse among marijuana-smokers (p < 0.01), cigarette-smokers (p < 0.01) and non-smokers-with-periodontitis (p < 0.01) than periodontally-healthy-non-smokers. Marijuana- and cigarette-smokers had Stage-IV/Grade C and non-smokers with periodontitis had Stage-III/Grade-C. Salivary IL-17A and IL-23 levels were higher in marijuana-smokers than cigarette-smokers (p < 0.01) and non-smokers-with-periodontitis (p < 0.01). Whole salivary IL-17A and IL-23 levels were higher among cigarette-smokers than non-smokers with periodontitis (p < 0.01) and periodontally-healthy-individuals (p < 0.01). Marijuana- and heavy cigarette-smokers have comparable clinicoradiographic periodontal statuses. This rejects hypothesis-1. However, whole salivary immunoinflammatory response may be moderately worse in marijuana-smokers compared with heavy cigarette-smokers and non-smoker with periodontitis thereby supporting hypothesis-2.
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Cannabis/efectos adversos , Interleucina-17/análisis , Interleucina-23/análisis , No Fumadores/estadística & datos numéricos , Saliva/inmunología , Fumadores/estadística & datos numéricos , Fumar/inmunología , Índice de Placa Dental , Humanos , Subunidad p19 de la Interleucina-23 , Masculino , Índice Periodontal , Periodontitis , Saliva/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: The diagnosis of primary Sjogren's syndrome (pSS) continues to be difficult and several patients keep symptomatic for years with different diagnoses before confirmation of pSS. Since the IL-23-IL-17 axis is involved in the etiopathogenesis of pSS we evaluated by immunohistochemistry and morphometric methods the presence of IL-17 as well as IL-23 within minor salivary glands (MSG) obtained from patients with uncertain diagnosis of pSS. MATERIALS AND METHODS: 42 patients, with symptoms attributable to pSS, and 8 patients used as a control, were enrolled for the study. Autoantibody detection, histological analysis for the presence of Germinal Centers (GC+), immunohistochemistry to detect IL-23 and IL-17 were performed. RESULTS: The detection of GC + anti-SSA and anti-SSB antibody in parallel with the detection of IL-17 and IL-23, displays only a diagnostic reinforcement value. Instead, the detection of a positive reaction for both IL-17 and IL-23 without GC + or autoantibody within minor salivary glands, as detected in 36 % of patients with uncertain diagnosis, may be hold as a sensitive and specific marker to identify those patients who are likely to evolve into pSS. CONCLUSION: we suggest to use the IL-17/ IL-23 immunohistochemical detection to improve the identification of patients with a possible diagnosis in all cases which do not fully meet the American-European criteria for pSS, in particular when the GC + are not present at histopathological analysis and anti-SSA and anti-SSB antibody are undetectable in the serum.