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1.
Allergol Immunopathol (Madr) ; 50(5): 162-168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36086977

RESUMO

BACKGROUND: Cow's milk protein allergy (CMPA) is an abnormal immune response caused by milk proteins and is most common in infancy and early childhood. Statistics revealed up to 7.5% of children suffered from milk allergy. Its clinical symptoms were characterized by diversity, non-specificity, and can affect multiple systems, including the digestive tract, skin, and respiratory tract. In this study, we aimed to investigate the effects of IL-12, IL-16, and IL-17A on diagnosing and monitoring CMPA in children for clinical treatment. METHODS: A total of 158 infants with CMPA and 89 healthy babies were recruited and evaluated. Demographic and clinical information of all participants were recorded. An extensive analysis of inflammatory cytokine levels, including IL-12, IL-16, and IL-17A, was performed in blood samples from 247 infants younger than 9 months. Meanwhile, the serological specificity immunoglobulin E (sIgE) levels were evaluated. In addition, the area under the curve (AUC) values of IL-12, IL-16, and IL-17A in differentiating CMP from healthy babies were measured by receiver operating characteristic analysis. Finally, the correlation between sIgE and IL-12, IL-16, and IL-17A levels were detected using Spearman correlation analysis. RESULTS: Compared with healthy control, infants who developed CMPA had decreased IL-12, increased IL-16, and IL-17A. Moreover, a significant correlation between serum IL-12, IL-16, IL-17A and sIgE levels was observed in the CMPA group. In addition, AUC values of IL-12, IL-16, and IL-17A in discriminating CMPA from healthy infants were 0.8425, 0.9196, and 0.8813, respectively. Finally, IL-12 was increased while IL-16 and IL-17A levels were decreased in the CMPA group after three months of milk avoidance treatment. CONCLUSIONS: We found that IL-12, IL-16, and IL-17A levels in children with CMPA were associated with SCORAD scores, sIgE levels, and disease severity, functioning as valuable disease-monitor markers in CMPA.


Assuntos
Hipersensibilidade a Leite , Animais , Biomarcadores , Bovinos , Feminino , Humanos , Interleucina-12 , Interleucina-16 , Interleucina-17
2.
J Immunol Res ; 2022: 6909764, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046722

RESUMO

Background: This study investigated whether vascular endothelial necroptosis is involved in deep vein thrombosis (DVT) and how IL-17B facilitates necroptosis signaling. Methods: The DVT mouse model was induced by ligation of the IVC. The cross-sectional area of thrombus increases and the thrombus occupied the entire venous lumen at 48 h after ligation. Meanwhile, the increased expression of p-RIP3/RIP3 was most pronounced at 48 h after ligation, and the p-MLKL/MLKL peaked at 72 h. Results: Based on Illumina sequencing and KEGG pathway analyses, the activated RIP3/MLKL is associated with increased IL-17B. With thrombus formation, IL-17B was upregulated and enhanced the expression of RIP3 and MLKL in the IVC wall, as well as their phosphorylation levels (all P < 0.05, the comparison group consisted of the control group, DVT group, DVT/IL-17B group, and DVT/anti-IL-17B group). The p-RIP3/RIP3 and p-MLKL/MLKL ratios were reduced by anti-IL-17B. Similarly, the weight and cross-sectional area of the thrombi were increased by IL-17B and decreased by the IL-17B antibody. IL-17B had a smaller effect on thrombosis in knockout mice compared with WT mice. In vitro, the IL-17B protein expression and the level of RIP3 and MLKL phosphorylation increased high in the OGD cells, accompanied by increased expression of IL-6 and TNF-α. IL-17B enhanced the expression of IL-6 and TNF-α but had little effect on the IL-6 and TNF-α after transfected with siRIP3 or siMLKL. Similarly, the plasma IL-17B, IL-6, and TNF-α were significantly increased after thrombosis in WT mice, and enhanced by IL-17B. But IL-17B did not increase the plasma IL-6 and TNF-α in knockout mice. Conclusions: In conclusion, those results suggest that vascular endothelial necroptosis plays a crucial role in vascular injury and IL-17B could enhance the necroptosis pathway.


Assuntos
Necroptose , Lesões do Sistema Vascular , Animais , Apoptose , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Knockout , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Mediators Inflamm ; 2022: 2222270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060927

RESUMO

Airway inflammation in asthma is managed with anti-inflammatory steroids such as dexamethasone (DEX). However, about 20% of asthmatics do not respond to this therapy and are classified as steroid-resistant. Currently, no effective therapy is available for steroid-resistant asthma. This work therefore evaluated the effect of a plant sterol, stigmasterol (STIG), and stigmasterol-dexamethasone combination (STIG+DEX) in LPS-ovalbumin-induced steroid-resistant asthma in Guinea pigs. To do this, the effect of drugs on inflammatory features such as airway hyperreactivity and histopathology of lung tissue was evaluated. Additionally, the possible pathway of drug action was assessed by measuring events such neutrophil levels, oxidative and nitrative stress, and histone deacetylase 2 (HDAC2) and interleukin 17 (IL-17) levels. STIG alone did not affect inflammatory features, although it caused some changes in the molecular events associated with steroid-resistant asthma. However, STIG+DEX caused significant modulation of inflammatory features by protecting against destruction of lung tissue. The modulation of inflammatory features was associated with significant inhibition of neutrophilia and oxidative and nitrative stress, decrease in HDAC2, and increase in IL-17 levels that are usually associated with steroid-resistant asthma. Our findings show that although STIG and DEX individually do not protect against steroid-resistant asthma, their coadministration results in significant modulation of inflammatory features and the associated molecular events that lead to steroid-resistant asthma.


Assuntos
Asma , Estigmasterol , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Dexametasona/uso terapêutico , Resistência a Medicamentos , Cobaias , Interleucina-17/uso terapêutico , Esteroides/farmacologia
4.
Biomed Res Int ; 2022: 4740141, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051483

RESUMO

Purpose: To identify the potential key genes and molecular pathways associated with keratoconus and allergic disease. Methods: The pubmed2ensembl database was used to identify the text mining genes (TMGs) collectively involved in keratoconus and allergic disease. The GeneCodis program was used to perform the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of TMGs. The protein-protein interaction (PPI) network of the TMGs was established by STRING; the significant gene modules and hub genes of PPI were further performed using the Cytoscape software. The DAVID database was used to perform the GO and KEGG analyses of the significant module. Results: In total, 98 TMGs collectively involved in keratoconus and allergic disease were identified. 19 enriched biological processes including 71 genes and 25 enriched KEGG pathways including 59 genes were obtained. A TMG PPI network was constructed, and 51 genes/nodes were identified with 110 edges; 3 most significant modules and 12 hub genes were chosen from the PPIs. GO enrichment analysis showed that the TMGs were primarily associated with collagen catabolic process, extracellular matrix organization and disassembly, cell adhesion and migration, collagen-containing extracellular matrix, extracellular matrix, and structure organization. KEGG pathway analysis showed that these DEGs were mainly involved in the IL-17 signaling pathway, inflammatory bowel disease, rheumatoid arthritis, allograft rejection, T cell receptor signaling pathway, cytokine-cytokine receptor interaction, and TNF signaling pathway. Conclusions: The results revealed that IL10, IL6, MMP9, MMP1, HGF, VEGFA, MMP3, MMP2, TGFB1, IL4, IL2, and IFNG were potential key genes involved in keratoconus. IL-17 signaling pathway was the potential pathways accounting for pathogenesis and development of keratoconus.


Assuntos
Biologia Computacional , Ceratocone , Biologia Computacional/métodos , Mineração de Dados , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Interleucina-17/genética , Ceratocone/genética , Mapas de Interação de Proteínas/genética
5.
BMC Genomics ; 23(1): 630, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056316

RESUMO

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is a common and organ-specific autoimmune disease. Early diagnosis and novel treatments are essential to improve the prognosis of TAO patients. Therefore, the current work was performed to identify the key genes and pathways for the biological and clinical implications of TAO through comprehensive bioinformatics analysis and a series of clinical validations. METHODS: GSE105149 and GSE185952 were obtained from the Gene Expression Omnibus (GEO) database for analysis. The data were normalized to identify the common differentially expressed genes (DEGs) between the two datasets, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to assess key pathways in TAO. Protein-protein interaction (PPI) networks and hub genes among the common DEGs were identified. Furthermore, we collected the general information and blood samples from 50 TAO patients and 20 healthy controls (HCs), and the expression levels of the proteins encoded by hub genes in serum were detected by enzyme-linked immunosorbent assay (ELISA). Then we further assessed the relationship between the ELISA data and the TAO development. RESULTS: Several common pathways, including neuroactive ligand-receptor interaction, the IL-17 signaling pathway, and the TNF signaling pathway, were identified in both datasets. In parallel, 52 common DEGs were identified. The KEGG analysis showed that these common DEGs are mainly enriched in long-term depression, the VEGF signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway, and cytokine-cytokine receptor interactions. The key hub genes PRKCG, OSM, DPP4, LRRTM1, CXCL6, and CSF3R were screened out through the PPI network. As confirmation, the ELISA results indicated that protein expression levels of PRKCG, OSM, CSF3R, and DPP4 were significantly upregulated in TAO patients compared with HCs. In addition, PRKCG and DPP4 were verified to show value in diagnosing TAO, and CSF3R was found to be a valuable diagnostic marker in distinguishing active TAO from inactive TAO. CONCLUSIONS: Inflammation- and neuromodulation-related pathways might be closely associated with TAO. Based on the clinical verification, OSM, CSF3R, CXCL6, DPP4, and PRKCG may serve as inflammation- or neuromodulation-related biomarkers for TAO, providing novel insights for the diagnosis and treatment of TAO.


Assuntos
Perfilação da Expressão Gênica , Oftalmopatia de Graves , Biologia Computacional/métodos , Dipeptidil Peptidase 4 , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Oftalmopatia de Graves/genética , Humanos , Inflamação , Interleucina-17 , Mapas de Interação de Proteínas
6.
PLoS One ; 17(9): e0274841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36136963

RESUMO

OBJECTIVES: T-helper 17 cell-mediated response and their effector IL-17 cytokine induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major cause of COVID-19 disease severity and death. Therefore, the study aimed to determine if IL-17 level in saliva mirrors its circulatory level and hence can be used as a non-invasive biomarker for disease severity. METHODS: Interleukin-17 (IL-17) level was evaluated by ELISA in saliva and blood of 201 adult COVID-19 patients with different levels of severity. The IL-17 saliva level was also associated with COVID-19 disease severity, and need for mechanical ventilation and/or death within 29 days after admission of severe COVID-19 patients. RESULTS: We found that IL-17 level in saliva of COVID-19 patients reflected its circulatory level. High IL-17 level in saliva was associated with COVID-19 severity (P<0.001), need for mechanical ventilation (P = 0.002), and/or death by 29 days (P = 0.002), after adjusting for patients' demographics, comorbidity, and COVID-19 serum severity markers such as D-Dimer, C-reactive protein, and ferritin. CONCLUSION: We propose that saliva IL-17 level could be used as a biomarker to identify patients at risk of developing severe COVID-19.


Assuntos
COVID-19 , Adulto , Biomarcadores , Proteína C-Reativa , COVID-19/diagnóstico , Citocinas , Ferritinas , Humanos , Interleucina-17 , SARS-CoV-2
7.
Parasite Immunol ; 44(10): e12942, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36054460

RESUMO

Experimental autoimmune encephalomyelitis (EAE) is an appropriate model for the study of the immunologic and pathologic mechanisms in multiple sclerosis (MS). According to the hygiene hypothesis, helminths can improve immunoregulation and have therapeutic effects on immune-mediated diseases. In this study, we used Dicrocoelium dendriticum (Dicrocoeliidae, Platyhelminthes) eggs for the evaluation of their prophylactic and treatment effects on EAE disease. D. dendriticum eggs were extracted. Female C57BL/6 mice were immunized with the specific antigen MOG35-55 , and then the egg extracts were utilized for prophylaxis and/or treatment. Clinical symptoms and other relevant parameters were assessed daily. The mRNA expression of transforming growth factor-ß (TGF-ß), interleukin-10 (IL-10), IL-6, IL-23 and IL-17 were assessed with a real-time polymerase chain reaction technique. Furthermore, secretion of TGF-ß and IL-17 cytokines were determined by enzyme-linked immunosorbent assay. Data indicated that clinical symptoms in prophylaxis and treatment groups were decreased significantly in comparison with the untreated control group (p < .001). Our results showed a significant decrease in IL-17, as well as an increase in TGF-ß cytokine in the treatment group compared to the EAE control group (p < .01). Furthermore, in the prophylaxis and treatment groups, the mRNA expression of disease-associated cytokines decreased and the mRNA expression of the anti-inflammatory cytokines increased. In this study, the D. dendriticum egg ameliorates the clinical symptoms of the EAE model through the modulation of related cytokines of Th17 and Treg cells. Therefore, using this parasite egg could be a new treatment for MS.


Assuntos
Dicrocoelium , Encefalomielite Autoimune Experimental , Animais , Anti-Inflamatórios , Citocinas/metabolismo , Dicrocoelium/genética , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Interleucina-17 , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro , Fator de Crescimento Transformador beta
8.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077306

RESUMO

The pharmacotherapy of inflammatory bowel disease (IBD) is still not fully effective and safe. Attempts to search for new IBD drugs remain an incessant research aim. One of the novel approaches is targeting the developmental pathway molecules and effector cytokines of Th17/Treg axis. This study aimed to elucidate the impact of new pyrrolo[3,4-d]pyridazinone derivatives, compounds 7b, 10b, or 13b, on the course of experimental colitis in rats and to assess whether these new compounds may influence Th17/Treg axis. Rats were pretreated with studied compounds intragastrically before intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid used for colitis induction. Body weight loss, disease activity index, colon index, and colon tissue damage were analyzed to evaluate the severity of colitis. The colonic levels of RORγt, STAT3, CCR6, Foxp3, IL-6, IL-10, IL-17, TNF-α, IL-23, and PGE2 were assessed. Pretreatment with compounds 7b and 13b alleviated the severity of colitis and concomitantly counteracted the increased levels of RORγt, STAT3, CCR6, IL-6, IL-17, IL-23, TNF-α, and PGE2. The beneficial effect of compounds 7b and 13b may be due to the decrease in the levels of Th17-specific transcription factors and cytokines. The studied compounds might therefore constitute a promising therapeutic strategy in Th17/Treg imbalance-driven inflammatory conditions such as IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Interleucina-6/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Oxidiazóis , Prostaglandinas E/efeitos adversos , Ratos , Fator de Transcrição STAT3/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Ácido Trinitrobenzenossulfônico/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo
9.
Sci Rep ; 12(1): 15578, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114367

RESUMO

Acute intoxication with diazinon (DZN) as a pesticide causes mortality and morbidity annually. This study shows the impact of sub-acute toxicity of DZN 20 mg/kg and the protective activities of chrysin (CH) as a flavone under the flavonoids family (12.5, 25 and 50 mg/kg) were assessed on BALB/c mouse immune system. The changes in morphological and functional properties of the immune system on thymus, spleen and liver histopathology, sub-populations of T lymphocytes, cytokines levels, transcription factors, complement function, phagocytosis, specific and total antibody productions were considered. The histopathological effects of DZN on the spleen and thymus were not significant, but the liver was damaged remarkably. In the presence of CH, the toxic effect of DZN is suppressed. DZN significantly decreased the number of whole blood TCD4+, TCD8+ and NK cells and suppressed the phagocytosis, delayed-type hypersensitivity (DTH) responses to sheep red blood cell (SRBC). Furthermore, it suppressed specific anti-SRBC-Ab, total IgG and IgM production, T-bet expression, and IFN-γ production. In contrast, DZN did not significantly affect complement function and the number of NK cells, TCD4+ and TCD8+ splenocytes. However, it potentiated the expression of GATA-3, ROR-γt and FOXP3 gene expression and consequently produced IL-4, IL-10, IL-17 and TGF-ß in whole blood. CH not only significantly increased the variables mentioned above at 12.5, 25 and 50 mg/kg but also could overcome the toxic effects of DZN on whole blood lymphocyte sub-populations and specific and total Ab production in 25 and 50 mg/kg concentrations, phagocytosis and DTH responses in 50 mg/kg, and modulation of the transcription factors and cytokine production, mainly in 25 and 50 mg/kg. In conclusion, DZN in sub-acute doses could remarkably deteriorate immune responses. However, CH can overcome the toxic effects of DZN on the immune components and functions of the immune system.


Assuntos
Flavonas , Praguicidas , Animais , Diazinon/toxicidade , Flavonoides/farmacologia , Fatores de Transcrição Forkhead , Imunoglobulina G , Imunoglobulina M , Interleucina-10 , Interleucina-17 , Interleucina-4 , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Ovinos , Fator de Crescimento Transformador beta
10.
Eur Respir Rev ; 31(165)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36130784

RESUMO

Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium Haemophilus influenzae. Here we review knowledge of non-typeable H. influenzae (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1ß, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically via upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Asma/complicações , Asma/diagnóstico , Asma/tratamento farmacológico , Molécula 1 de Adesão Celular , Citocinas , Haemophilus influenzae , Humanos , Inflamassomos , Interleucina-12 , Interleucina-17/metabolismo , Interleucina-6 , Interleucina-8 , Macrolídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doença Pulmonar Obstrutiva Crônica/metabolismo , Sistema Respiratório , Fatores de Necrose Tumoral
11.
Mediators Inflamm ; 2022: 8285084, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117588

RESUMO

In the Brazilian Amazon, the snake Bothrops atrox is the primary cause of snakebites. B. atrox (BaV) venom can cause systemic pathophysiological changes such as acute kidney injury (AKI), which leads to the production of chemokines and cytokines in response to the envenomation. These soluble immunological molecules act by modulating the inflammatory response; however, the mechanisms associated with the development of AKI are still poorly understood. Here, we characterize the profile of these soluble immunological molecules as possible predictive biomarkers of the development of AKI. The study involved 34 patients who had been victims of snakebites by Bothrops sp. These were categorized into two groups according to the development of AKI (AKI(-)/AKI(+)), using healthy donors as the control (HD). Peripheral blood samples were collected at three-time points: before antivenom administration (T0) and at 24 and 48 hours after antivenom (T1 and T2, respectively). The soluble immunological molecules (CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-γ, IL-4, and IL-17A) were quantified using cytometric bead array. Our results demonstrated an increase in CXCL-9, CXCL-10, IL-6, IL-2, IL-10, and IL-17A molecules in the groups of patients who suffered Bothrops snakebites (AKI(-) and AKI(+)) before antivenom administration, when compared to HD. In the AKI(+) group, levels of CXCL-8 and CCL-2 molecules were elevated on admission and progressively decreased during the clinical evolution of patients after antivenom administration. In addition, in the signature analysis, these were produced exclusively by the group AKI(+) at T0. Thus, these chemokines may be related to the initiation and extension of AKI after envenomation by Bothrops and present themselves as two potential biomarkers of AKI at T0.


Assuntos
Injúria Renal Aguda , Bothrops , Mordeduras de Serpentes , Animais , Antivenenos/uso terapêutico , Biomarcadores , Quimiocinas , Citocinas , Interleucina-10 , Interleucina-17 , Interleucina-2 , Interleucina-4 , Interleucina-6 , Prognóstico , Mordeduras de Serpentes/complicações
12.
J Immunol Res ; 2022: 2787954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118416

RESUMO

Cytokines like IL-17A have been consistently found to be elevated in psoriatic lesional skin, and therapeutic antibodies to IL-17 have demonstrated efficacy in treating psoriatic skin and joint disease. However, results about the circulating cytokines in psoriasis patients remained controversial. Anticytokine autoantibodies (ACAAs) were detected in various autoimmune diseases but remained largely unknown in psoriasis. We aimed to investigate the serum levels of cytokines and ACAAs in psoriasis patients. The study included 44 biologics-naive psoriasis patients and 40 healthy controls. Serum cytokines and the corresponding autoantibodies were measured by multiplex bead-based technology. The bioactivity of serum IL-17A was determined by IL-8 production in primary keratinocytes. Herein, we found serum levels of IL-12B (median: 6.16 vs. 9.03, p = 0.0194) and Th17 cytokines (IL-17A: median: 0.32 vs. 1.05, p = 0.0026; IL-22: median: 4.41 vs. 4.41, p = 0.0120) were increased in psoriasis patients. More interestingly, bioactive IL-17A was identified in a proportion of patients and positively correlated with disease severity. A few of cytokines were closely associated with each other and formed into a distinct panel in psoriasis. Of 13 anticytokine antibodies, anti-IL-22 was moderately lower (median: 262.8 vs.190.5, p = 0.0418), and anti-IL-15 was slightly higher (median: 25.5 vs. 30.5, p = 0.0069) in psoriasis than controls. None of ACAAs was related to disease severity. Consequently, the ratios of antibodies to cytokines varied with the pattern of cytokines. In summary, our finding suggested that the levels of circulating bioactive IL-17A were associated with disease activity in psoriasis patients. In contrast, the titers of ACAAs were not significantly altered nor correlated with disease severity. However, the functionality of ACAAs remains to be further demonstrated in vitro in future studies.


Assuntos
Produtos Biológicos , Psoríase , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Autoanticorpos , Produtos Biológicos/uso terapêutico , Citocinas , Humanos , Interleucina-17 , Interleucina-8 , Psoríase/tratamento farmacológico
13.
Contrast Media Mol Imaging ; 2022: 4421418, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159171

RESUMO

In order to explore the risk factors of infertility caused by endometriosis (EMT) and their correlation with vascular endothelial growth factor (VEGF), TNF-α, IL-6, IL-10, and IL-17, endometriosis sufferers admitted to our hospital from January 2021 to May 2022 are selected to conduct the examination. According to the pregnancy of patients, patients were included in the simple EMT set and EMT combined infertility set, with 50 cases in each group. The degree of dysmenorrhea is evaluated by the VAS score, and Luminex liquid protein is used to analyze the standards of the tumor necrosis factor (TNF-A), interleukin (IL)-10, IL-6, IL-17, and VEGF. Logistic multifactor regression decomposition is applied to analyze the risk factors of infertility in EMT sufferers. Besides, the standards of VEGF, TNF-α, IL-6, IL-10, and IL-17 in sufferers with different periods/agony degrees are evaluated, and the correlation of different periods/agony degrees with VEGF, TNF-α, IL-6, IL-10, and IL-17 is analyzed. The results show that the different R-AFS periods are notoriously positively correlated with VEGF, TNF-α, IL-6, IL-10, and IL-17 (all P < 0.05), and the VAS score is notoriously positively correlated with the abovementioned factors.


Assuntos
Endometriose , Infertilidade , Endometriose/metabolismo , Feminino , Humanos , Interleucina-10 , Interleucina-17 , Interleucina-6/metabolismo , Gravidez , Fatores de Risco , Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
14.
Front Immunol ; 13: 932393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159826

RESUMO

Although studies have identified the presence of gut-associated cells in the enthesis of joints affected by spondylarthritis (SpA), a direct link through cellular transit between the gut and joint has yet to be formally demonstrated. Using KikGR transgenic mice to label in situ and track cellular trafficking from the distal colon to the joint under inflammatory conditions of both the gut and joint, we demonstrate bona-fide gut-joint trafficking of T cells from the colon epithelium, also called intraepithelial lymphocytes (IELs), to distal sites including joint enthesis, the pathogenic site of SpA. Similar to patients with SpA, colon IELs from the TNFΔARE/+ mouse model of inflammatory bowel disease and SpA display heightened TNF production upon stimulation. Using ex vivo stimulation of photo-labeled gut-joint trafficked T cells from the popliteal lymph nodes of KikGR and KikGR TNFΔARE/+ we saw that the CD4+ photo-labeled population was highly enriched for IL-17 competence in healthy as well as arthritic mice, however in the TNFΔARE/+ mice these cells were additionally enriched for TNF. Using transfer of magnetically isolated IELs from TNF+/+ and TNFΔARE/+ donors into Rag1 -/- hosts, we confirmed that IELs can exacerbate inflammatory processes in the joint. Finally, we blocked IEL recruitment to the colon epithelium using broad spectrum antibiotics in TNFΔARE/+ mice. Antibiotic-treated mice had reduced gut-joint IEL migration, contained fewer Il-17A and TNF competent CD4+ T cells, and lessened joint pathology compared to untreated littermate controls. Together these results demonstrate that pro-inflammatory colon-derived IELs can exacerbate inflammatory responses in the joint through systemic trafficking, and that interference with this process through gut-targeted approaches has therapeutic potential in SpA.


Assuntos
Interleucina-17 , Espondilartrite , Animais , Antibacterianos , Citocinas , Proteínas de Homeodomínio , Inflamação , Camundongos , Camundongos Transgênicos , Espondilartrite/terapia
15.
Front Immunol ; 13: 900273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159856

RESUMO

Background: The interleukin-17 (IL-17) family contains six homologous genes, IL-17A to IL-17F. Growing evidence indicates that dysregulated IL-17 family members act as major pathogenic factors in the early and late stages of cancer development and progression. However, the prevalence and predictive value of IL-17 for immune checkpoint inhibitor (ICI) therapeutic effectiveness in multiple tumor types remain largely unknown, and the associations between its expression levels and immunotherapy-associated signatures also need to be explored. Methods: The pan-cancer dataset in The Cancer Genome Atlas (TCGA) was downloaded from UCSC Xena (http://xena.ucsc.edu/). The immunotherapeutic cohorts included IMvigor210, which were obtained from the Gene Expression Omnibus database and included in a previously published study. Other datasets, namely, the GEO dataset and PRECOG, GEO, and METABRIC databases, were also included. In 33 TCGA tumor types, a pan-cancer analysis was carried out including their expression map, clinical risk assessment, and immune subtype analysis, along with their association with the stemness indices, tumor microenvironment (TME) in pan-cancer, immune infiltration analysis, ICI-related immune indicators, and drug sensitivity. RT-PCR was also carried out to verify the gene expression levels among MCF-10A and MCF-7 cell lines. Results: The expression of the IL-17 family is different between tumor and normal tissue in most cancers, and consistency has been observed between gene activity and gene expression. RT-PCR results show that the expression differences in the IL-17 family of human cell (MCF-10A and MCF-7) are consistent with the bioinformatics differential expression analysis. Moreover, the expression of the IL-17 family can be a sign of patients' survival prognosis in some tumors and varies in different immune subtypes. Moreover, the expression of the IL-17 family presents a robust correlation with immune cell infiltration, ICI-related immune indicators, and drug sensitivity. High expression of the IL-17 family is significantly related to immune-relevant pathways, and the low expression of IL-17B means a better immunotherapeutic response in BLCA. Conclusion: Collectively, IL-17 family members may act as biomarkers in predicting the prognosis of the tumor and the therapeutic effects of ICIs, which provides new guidance for cancer treatment.


Assuntos
Interleucina-17 , Neoplasias , Biomarcadores , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Interleucina-17/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Microambiente Tumoral/genética
16.
Oxid Med Cell Longev ; 2022: 6060677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160710

RESUMO

Cinnamomi Ramulus (CR) has been extensively used as a remedy for inflammatory diseases in China. This study adopted an integrative approach of experimental research, phytochemistry, and network pharmacology to investigate its alleviative effects on rheumatoid arthritis (RA) and the underlying potential mechanisms. CR extract (50, 100, and 200 mg/kg) and methotrexate (MTX) significantly ameliorated RA symptoms in the collagen-induced arthritis (CIA) rat model. They also reduced paw volume, arthritis index, proinflammatory cytokines (TNF-α, IL-17A, IL-6, and IL-1ß), and oxidative damage. Sixty-three compounds were systematically identified as the basic components of CR. Fifty-five common genes obtained from compounds and GEO databases were employed to construct the protein-protein interaction (PPI) network. Among them, 20 hub genes were identified via the cytoHubba. Enrichment analysis of the common genes indicated that the TNF signaling pathway and IL-17 signaling pathway might be the potential key pathways. Moreover, molecular docking methods confirmed the high affinity between the top 10 bioactive components of CR and the top 10 targets. In addition, in vitro results showed that CR extract (0.2, 0.4, and 0.8 mg/mL) inhibited inflammation and oxidative damage in MH7A cells stimulated by lipopolysaccharide (LPS). In summary, this study adopted multiple approaches to elucidate the protective effect and potential mechanisms of CR on RA, indicating that CR might be a promising herbal candidate for further investigation of RA treatment.


Assuntos
Artrite Experimental , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Animais , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-17/genética , Interleucina-6 , Lipopolissacarídeos/uso terapêutico , Metotrexato , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ratos , Fator de Necrose Tumoral alfa
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(10): 872-879, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36163617

RESUMO

Objectives To investigate the effect of the imbalance of Th17/Treg on egg granuloma formation of liver with Schistosomiasis japonicum. Methods The BALB/c mice were infected with Schistosoma japonicum cercariae to establish a model of Schistosomiasis japonica. The blood samples, liver tissues and spleen tissue were harvested at the 2nd, 4th, 6th, 8th week, respectively. HE staining and Masson staining were performed to assess the pathological characteristics of the liver. Flow cytometry (FCM) was conducted to evaluate the proportion of CD4+ T cell subsets including Th17 cells and Tregs in liver and spleen tissue. The quantitative real-time PCR (qRT-PCR) was carried out to investigate the mRNA level of cytokines including RORγt, FOXP3, IL-6, IL-17, IL-23 and IL-10 in liver tissues. Finally, ELISA was performed to assess the serum level of cytokines including IL-6, IL-17, IL-23 and TGF-ß. Schistosoma japonicium soluble egg antigen (SjSEA) were prepared to stimulate mouse spleen cells in vitro. qRT-PCR was carried out to investigate the mRNA level of cytokine including RORγt and FOXP3 and ELISA was performed to assess the expression level of cytokines including IL-6, IL-17, IL-23 and TGF-ß at different time points. Results HE and Masson staining demonstrated that inflammatory cell infiltration, schistosome egg granuloma formation and the collagen deposition increased in the liver tissue after the 4th week. The longer the infection, the more severe the liver pathology. In the liver and spleen tissues, the percentage of Th17 cells of infection group (2nd, 4th and 6th weeks) were significantly higher than the healthy group. The percentage of Tregs in the liver tissues of infection group (4th, 6th and 8th weeks) were significantly higher than the healthy group, and the percentage of Tregs in the spleen of infection group (2nd and 4th weeks) were significantly higher than the healthy group. Th17/Treg ratios in the liver of infection group were lower than the healthy group. Th17/Treg ratios in the spleen of infection group (2nd and 4th weeks) were lower than the healthy group, while it increased in the 6th week. At the same time, the levels of Th17 cells and Tregs related nuclear transcription factors and cytokines showed similar dynamic changes as the percentages of T cell subsets. SjSEA can induce the differentiation of Th17 and Tregs and the expression of related cytokines and transcription factors. Conclusion Th17 cells may play a major role in liver pathology, and the imbalance of Th17 cells/Tregs was closely related to the schistosome egg granuloma formation.


Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Animais , Citocinas/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Granuloma/metabolismo , Granuloma/patologia , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Interleucina-6/metabolismo , Fígado , Camundongos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , RNA Mensageiro/metabolismo , Schistosoma japonicum/metabolismo , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/patologia , Linfócitos T Reguladores , Células Th17 , Fator de Crescimento Transformador beta/metabolismo
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(10): 880-885, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36163618

RESUMO

Objective To investigate the protective effect and mechanism of recombinant human interleukin 35(rhIL-35) on coronary artery injury in Kawasaki disease (KD). Methods Human coronary artery endothelial cells (HCAECs) were cultured in vitro to establish KD vascular model. Tumor necrosis factor α(TNF-α) and the serum of KD patients stimulated HCAECs were used to mimic the local inflammatory lesions of KD. The cells were divided into control group, TNF-α and KD serum stimulation group, (25, 50) ng/mL rhIL-35 treatment group. Cell proliferation was detected by CCK-8 assay; mRNA levels of IL-1ß, IL-6, IL-17A and zonula occludens-1(ZO-1) of HCAECs were detected by real-time quantitative PCR; IL-35 expression in plasma and IL-1ß, IL-6 and IL-17A content in HCAEC supernatant were tested by ELISA; Western blot was performed to detect the expression of nuclear factor κB p65 (NF-κB p65) and ZO-1. Results TNF-α and KD serum inhibited the proliferation of HCAECs, while rhIL-35 significantly reversed the above effects. RhIL-35 significantly down-regulated the expression of IL-1ß, IL-6 and IL-17A after preconditioning HCAECs. Compared with TNF-α and KD serum stimulation group, rhIL-35 pretreated cells could significantly increase ZO-1 protein expression and inhibit NF-κB p65 expression. Conclusions rhIL-35 can alleviate the damage of KD coronary artery endothelial cells by inhibiting NF-κB pathway.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Humanos , Interleucina-17/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucinas/metabolismo , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Sincalida/metabolismo , Sincalida/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
19.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(10): 893-897, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36163620

RESUMO

Objective To explore the role of regulatory T cells (Tregs) and its related cytokines in mouse model of psoriasis induced by imiquimod. Methods Female BALB/c mice were divided into control group and model group of psoriasis induced by imiquimod, with ten mice in each group. The psoriasis model was established by smearing imiquimod cream on the back of mice. HE staining was performed to observe the pathological changes of skin tissues. Flow cytometry was used to detect the number of Tregs in spleen and the levels of serum IL-10 and TGF-ß1 was detected by ELISA. Results The mouse model of psoriasis was successfully established. Compared with the control group, the percentage of Tregs in spleen of the mouse model group significantly increased, and the levels of serum IL-10 and TGF-ß1 also increased. Conclusion The number of Tregs and related cytokines increase in mouse model of psoriasis.


Assuntos
Interleucina-10 , Psoríase , Animais , Citocinas , Modelos Animais de Doenças , Feminino , Imiquimode/efeitos adversos , Interleucina-17 , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Psoríase/patologia , Pele , Baço/patologia , Linfócitos T Reguladores , Fator de Crescimento Transformador beta1
20.
Clin Lymphoma Myeloma Leuk ; 22 Suppl 2: S348-S349, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36164030

RESUMO

CONTEXT: Classic Hodgkin lymphoma (cHL) is a phenotypically heterogeneous disease with enigmatic biology and pathogenesis. By leveraging ctDNA analysis, here we identify molecular groups of cHL with phenotype- and outcome-associated signatures. OBJECTIVE: Identification and biological characterization of novel cHL subgroups. METHODS: We sequenced 202 cHL patients targeting ~344 kb of genomic space. The length of ctDNA mapped reads was extracted, and unsupervised clustering was performed. PET/CT scan and 71 plasma cytokines were obtained for clinical correlation. Single-cell RNA sequencing was performed for 8 patients. RESULTS: To identify molecular subgroups within cHL, we focused on the fragmentation profile of cfDNA, a non-genetic way of detecting tumor-derived DNA in the cfDNA samples. We identified two distinct clusters, one with a fragmentation profile close to healthy (N=135), named mono-nucleosomal, and a submono-nucleosomal cluster characterized by a global shift toward shorter fragments, whose length was less than the typical wrap around the nucleosome (N=67). We explored whether cHL subtypes defined by the cfDNA fragmentation profile are clinically and biologically validated. Patients with the submono-nucleosomal fragmentome showed more frequent advanced-stage B symptoms and elevated ESR at the clinical level, higher tumor volume (TMTV and TLG) at the radiomic level, and lower PFS in terms of outcome. Tumor mutations and immune microenvironment are pathophysiologic features of cHL. The submono-nucleosomal cluster carried a higher tumor mutation burden because of heavier aberrant somatic hypermutation (ASHM). The submono-nucleosomal cluster had an immune-suppressive microenvironment enriched of T-regs and higher plasmatic levels of T-regs chemoattractants and inducers of PD1 expression (IL6, CCL2, CCL4). Conversely, mono-nucleosomal cHL had a microenvironment enriched of TFH cells and cytotoxic CD8 TEM cells and associated with cytokines and chemokines that are known for being attractants and activators of effector T cells (IL-1a, CCL21, CXCL12, IL-17A). CONCLUSIONS: Our observations indicate that cHL subgroups belonging to the submono-nucleosomal cluster have a more aggressive disease, a higher mutation load and more neoantigens likely due to denser ASHM, and an immune-suppressive microenvironment. Instead, cHL subgroups belonging to the mono-nucleosomal cluster have a less aggressive disease, a lower mutation load and lower neoantigens likely due to lighter ASHM, and a tumor-suppressive microenvironment.


Assuntos
Ácidos Nucleicos Livres , Doença de Hodgkin , Fatores Quimiotáticos , Doença de Hodgkin/patologia , Humanos , Interleucina-17/genética , Interleucina-6/genética , Nucleossomos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Microambiente Tumoral/genética
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