Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20.302
Filtrar
1.
Mediators Inflamm ; 2024: 3282679, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962170

RESUMO

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL-35 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T-cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL-35-mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL-35, a colitis model was successfully induced by giving BALB/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia/IL-35, empty plasmid-transformed Pichia (Pichia/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL-35 treatment was detected. After administration of Pichia/IL-35, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia/IL-35 treatment group was alleviated. Notably, Pichia/IL-35 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL-6 in the colon. With Pichia/IL-35 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. In vitro experiments, IL-35 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia/IL-35 group also expressed more TCPTP than that of the untreated group and the Pichia/0 group.


Assuntos
Interleucinas , Macrófagos , Camundongos Endogâmicos BALB C , Animais , Camundongos , Interleucinas/metabolismo , Macrófagos/metabolismo , Células RAW 264.7 , Colite/induzido quimicamente , Colite/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Colite Ulcerativa/metabolismo , Colite Ulcerativa/induzido quimicamente , Masculino , Regulação para Cima , Saccharomycetales
2.
Front Immunol ; 15: 1395921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966644

RESUMO

IL-27, a member of the IL-6/IL-12 cytokine superfamily, is primarily secreted by antigen presenting cells, specifically by dendric cells, macrophages and B cells. IL-27 has antiviral activities and modulates both innate and adaptive immune responses against viruses. The role of IL-27 in the setting of viral infections is not well defined and both pro-inflammatory and anti-inflammatory functions have been described. Here, we discuss the latest advancements in the role of IL-27 in several viral infection models of human disease. We highlight important aspects of IL-27 expression regulation, the critical cell sources at different stages of the infection and their impact in cell mediated immunity. Lastly, we discuss the need to better define the antiviral and modulatory (pro-inflammatory vs anti-inflammatory) properties of IL-27 in the context of human chronic viral infections.


Assuntos
Imunidade Adaptativa , Viroses , Humanos , Viroses/imunologia , Animais , Regulação da Expressão Gênica , Interleucina-27/metabolismo , Vírus/imunologia , Interleucinas/imunologia , Interleucinas/metabolismo
3.
J Immunol Res ; 2024: 9527268, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966668

RESUMO

Aberrant accumulation of circulating follicular helper T cells (cTfh) has been found in the peripheral blood mononuclear cells (PBMCs) of Graves' disease (GD) patients. However, the underlying mechanism that contributes to the imbalance of cTfh cells remains unknown. Previously, studies described a GD-related circular RNAs (circRNAs)-circZNF644 that might be associated with cTfh cells. This study aimed to investigate the role of circZNF644 on cTfh cells in GD patients. Here, we found that circZNF644 was highly stable expression in the PBMCs of GD patients, which was positively correlated with the serum levels of TSH receptor autoantibodies (TRAb). Knockdown of circZNF644 caused a reduction of the proportion of cTfh cells in vitro. Mechanistically, circZNF644 served as a ceRNA for miR-29a-3p to promote ICOS expression, resulting in increased cTfh cells. In the PBMCs of GD patients, circZNF644 expression was positively correlated with ICOS expression and the percentage of cTfh cells, but negatively related to miR-29a-3p expression. Additionally, a strong relationship between circZNF644 and IL-21 was revealed in GD patients, and silencing of circZNF644 inhibited IL-21 expression. Our study elucidated that elevated expression of circZNF644 is a key feature in the development of GD and may contribute to the pathogenic role of cTfh cells in GD.


Assuntos
Doença de Graves , MicroRNAs , RNA Circular , Células T Auxiliares Foliculares , Humanos , Doença de Graves/genética , Doença de Graves/imunologia , RNA Circular/genética , Masculino , Feminino , Células T Auxiliares Foliculares/imunologia , Adulto , MicroRNAs/genética , Pessoa de Meia-Idade , Autoanticorpos/imunologia , Autoanticorpos/sangue , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Interleucinas/genética , Interleucinas/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Regulação da Expressão Gênica
4.
Mol Med Rep ; 30(3)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38994764

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive form of cancer with a low survival rate. A successful treatment strategy should not be limited to targeting cancer cells alone, but should adopt a more comprehensive approach, taking into account other influential factors. These include the extracellular matrix (ECM) and immune microenvironment, both of which are integral components of the tumor microenvironment. The present review describes the roles of pancreatic stellate cells, differentiated cancer­associated fibroblasts and the interleukin family, either independently or in combination, in the progression of precursor lesions in pancreatic intraepithelial neoplasia and PDAC. These elements contribute to ECM deposition and immunosuppression in PDAC. Therapeutic strategies that integrate interleukin and/or stromal blockade for PDAC immunomodulation and fibrogenesis have yielded inconsistent results. A deeper comprehension of the intricate interplay between fibrosis, and immune responses could pave the way for more effective treatment targets, by elucidating the mechanisms and causes of ECM fibrosis during PDAC progression.


Assuntos
Carcinoma Ductal Pancreático , Fibrose , Interleucinas , Neoplasias Pancreáticas , Células Estreladas do Pâncreas , Microambiente Tumoral , Humanos , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Microambiente Tumoral/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Interleucinas/metabolismo , Interleucinas/imunologia , Animais , Matriz Extracelular/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia
6.
J Exp Med ; 221(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38949650

RESUMO

Germline activating mutations in STAT3 cause a multi-systemic autoimmune and autoinflammatory condition. By studying a mouse model, Toth et al. (https://doi.org/10.1084/jem.20232091) propose a role for dysregulated IL-22 production by Th17 cells in causing some aspects of immune-mediated skin inflammation in human STAT3 GOF syndrome.


Assuntos
Interleucina 22 , Fator de Transcrição STAT3 , Pele , Células Th17 , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Animais , Humanos , Células Th17/imunologia , Células Th17/metabolismo , Pele/metabolismo , Pele/patologia , Interleucinas/genética , Interleucinas/metabolismo , Mutação com Ganho de Função , Camundongos , Inflamação/metabolismo
7.
PLoS Pathog ; 20(7): e1012302, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949991

RESUMO

Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that the combined actions of both cytokines are essential for resistance to OPC. Mice lacking IL-17RA and IL-22RA1 exhibited high fungal loads in esophagus- and intestinal tract, severe weight loss, and symptoms of colitis. Ultimately, mice succumbed to infection. Dual loss of IL-17RA and IL-22RA impaired expression of small proline rich proteins (SPRRs), a class of antimicrobial effectors not previously linked to fungal immunity. Sprr2a1 exhibited direct candidacidal activity in vitro, and Sprr1-3a-/- mice were susceptible to OPC. Thus, cooperative actions of Type 17 cytokines mediate oral mucosal anti-Candida defenses and reveal a role for SPRRs.


Assuntos
Candidíase Bucal , Interleucina-17 , Interleucina 22 , Interleucinas , Camundongos Knockout , Animais , Camundongos , Candida albicans/imunologia , Candidíase Bucal/imunologia , Candidíase Bucal/microbiologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Interleucinas/imunologia , Interleucinas/metabolismo , Camundongos Endogâmicos C57BL , Receptores de Interleucina/imunologia , Receptores de Interleucina/metabolismo , Receptores de Interleucina-17/imunologia , Receptores de Interleucina-17/metabolismo
8.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(7): 653-662, 2024 Jul 09.
Artigo em Chinês | MEDLINE | ID: mdl-38949133

RESUMO

Objective: To investigate the regulatory effect and mechanism of interleukin-22 (IL-22) on the gingival epithelial barrier in the context of periodontal inflammation. Methods: IL-22 knockout (IL-22 KO) mice were constructed, and periodontitis mice models were established through oral gavage with polymicrobial inoculation. DNAs were extracted from the oral plaques of IL-22 KO periodontitis mice group (n=7) and their wild-type littermates periodontitis group (n=7) to establish a periodontitis-related oral microbiota database"PD-RiskMicroDB", determining the relationship between changes in oral microbiota and microbial function in two groups using 16S rRNA sequencing results. Gingival epithelial cells (GEC) were cultured by modified trypsinization method, and were stimulated with 100 µg/L IL-22, Porphyromonas gingivalis (Pg) (multiplicity of infection:100), separately or together for 3 and 12 hours. The experimental groups were as follows: control group (no stimulation), IL-22 group, Pg group and Pg+IL-22 group. The expression of barrier protein E-cadherin in each group at 3 h was detected by immunofluorescence, real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Fluorescein isothiocyanate-dextran-mediated epithelial cell permeability experiment was conducted to clarify the changes in permeability of GEC in each group at 3 and 12 h. The mRNA expressions of E-cadherin in the gingival epithelium of wild-type littermates periodontitis group and IL-22 KO periodontitis group were detected by RT-qPCR. Fifteen C57BL/6 wild-type mice were randomly divided into control group (n=5), periodontitis group (n=5) and periodontitis+IL-22 treatment group (n=5). RT-qPCR and immunohistochemistry (IHC) staining were used to detect the expression level of E-cadherin in the gingival epithelium of each group. Results: 16S rRNA sequencing results showed that the composition of oral microbiota changed in IL-22 KO periodontitis group, of which the abundance of bacterial genera related to periodontal tissue invasion was significantly increased (linear discriminant analysis score: 2.22, P=0.009), compared with wild-type littermates periodontitis group. In vitro cell experiments showed that after Pg infection for 3 hours, the cell connections of GEC in Pg group were interrupted, and the fluorescence intensity of E-cadherin was reduced in Pg group compared with the control group. Meanwhile, the mRNA and protein expression levels of E-cadherin (mRNA: 0.69±0.12; protein: 0.60±0.12) were downregulated compared with the control group [mRNA: 1.00±0.00 (P=0.043); protein: 1.04±0.08 (P=0.003)], respectively. The fluorescence intensity of E-cadherin in the Pg+IL-22 group was enhanced compared with Pg group, and expression levels of E-cadherin mRNA (1.16±0.10) and protein (0.98±0.07) in Pg+IL-22 group showed a significant increase compared with Pg group [mRNA: 0.69±0.12 (P=0.005); protein: 0.60±0.12 (P=0.007)]. The result of epithelial permeability test showed that there was no statistical difference in epithelial permeability among control group, Pg group, IL-22 group and Pg+IL-22 group with treatment for 3 hours (F=0.20, P=0.893). While when the treatment time turned to be 12 hours, the epithelial barrier permeability showed a significant increase in Pg group (1.39±0.15) compared with control group (1.00±0.00, P=0.027), and a decrease in Pg+IL-22 group (1.02±0.18) compared with Pg group (1.39±0.15, P=0.034). In vivo, the mRNA expression of E-cadherin in the gingival epithelium of IL-22 KO periodontitis group decreased significantly (0.32±0.21) compared with wild-type littermates periodontitis group (1.01±0.01) (t=5.70, P=0.005). Moreover, RT-qPCR and IHC staining results showed that the mRNA expression level of E-cadherin (0.40±0.07) and absorbance value of E-cadherin positive expression (0.02±0.00) in gingival epithelial tissue of periodontitis group were both significantly down-regulated compared with control group [mRNA: 1.00±0.00 (P=0.005); absorbance value of E-cadherin positive expression: 0.04±0.01 (P=0.006)]. Meanwhile, the mRNA expression level of E-cadherin (1.06±0.24) and the absorbance value of E-cadherin positive expression (0.03±0.01) were both observed increase in periodontitis+IL-22 treatment group compared with periodontitis group (P=0.003, P=0.039). Conclusions: IL-22 may exert a protective effect on the gingival epithelial barrier in an inflammatory environment by regulating the invasiveness of oral microbiota and the expression of host barrier protein.


Assuntos
Caderinas , Gengiva , Interleucina 22 , Interleucinas , Camundongos Knockout , Microbiota , Periodontite , Porphyromonas gingivalis , Animais , Interleucinas/metabolismo , Caderinas/metabolismo , Gengiva/citologia , Gengiva/metabolismo , Gengiva/microbiologia , Camundongos , Periodontite/microbiologia , Periodontite/metabolismo , Células Epiteliais/metabolismo , RNA Ribossômico 16S
9.
Respir Res ; 25(1): 275, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003443

RESUMO

Pleurisy can be categorized as primary or secondary, arising from immunological, tumorous, or microbial conditions. It often results in lung structure damage and the development of various respiratory issues. Among the different types, tuberculous pleurisy has emerged as a prominent focus for both clinical and scientific investigations. The IL-10 family, known for its anti-inflammatory properties in the human immune system, is increasingly being studied for its involvement in the pathogenesis of pleurisy. This review aims to present a detailed overview of the intricate role of IL-10 family members (specifically IL-10, IL-22, and IL-26) in human and animal pleuritic diseases or relevant animal models. These insights could serve as valuable guidance and references for further studies on pleurisy and potential therapeutic strategies.


Assuntos
Interleucina-10 , Interleucina 22 , Interleucinas , Tuberculose Pleural , Humanos , Tuberculose Pleural/diagnóstico , Tuberculose Pleural/imunologia , Tuberculose Pleural/metabolismo , Tuberculose Pleural/tratamento farmacológico , Interleucinas/metabolismo , Interleucinas/imunologia , Animais , Interleucina-10/metabolismo , Pleurisia/imunologia , Pleurisia/diagnóstico , Pleurisia/metabolismo
10.
Front Immunol ; 15: 1338585, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994359

RESUMO

Regular assessment of disease activity in relapsing-remitting multiple sclerosis (RRMS) is required to optimize clinical outcomes. Biomarkers can be a valuable tool for measuring disease activity in multiple sclerosis (MS) if they reflect the pathological processes underlying MS pathogenicity. In this pilot study, we combined multiple biomarkers previously analyzed in RRMS patients into an MS disease activity (MSDA) score to evaluate their ability to predict relapses and treatment response to glatiramer acetate (GA). Response Gene to Complement 32 (RGC-32), FasL, IL-21, SIRT1, phosphorylated SIRT1 (p-SIRT1), and JNK1 p54 levels were used to generate cut-off values for each biomarker. Any value below the cutoff for RGC-32, FasL SIRT1, or p-SIRT1 or above the cutoff for IL-21 or JNK1 p54 was given a +1 value, indicating relapse or lack of response to GA. Any value above the cutoff value for RGC-32, FasL, SIRT1, p-SIRT1 or below that for IL-21 or JNK1 p54 was given a -1 value, indicating clinical stability or response to GA. An MSDA score above +1 indicated a relapse or lack of response to treatment. An MSDA score below -1 indicated clinical stability or response to treatment. Our results showed that the MSDA scores generated using either four or six biomarkers had a higher sensitivity and specificity and significantly correlated with the expanded disability status scale. Although these results suggest that the MSDA test can be useful for monitoring therapeutic response to biologic agents and assessing clinically challenging situations, the present findings need to be confirmed in larger studies.


Assuntos
Biomarcadores , Acetato de Glatiramer , Sirtuína 1 , Humanos , Masculino , Adulto , Feminino , Sirtuína 1/metabolismo , Acetato de Glatiramer/uso terapêutico , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Proteína Ligante Fas/metabolismo , Resultado do Tratamento , Projetos Piloto , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Interleucinas , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/diagnóstico , Índice de Gravidade de Doença , Imunossupressores/uso terapêutico
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 744-748, 2024 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-38948276

RESUMO

Objective: To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis (AS), to unveil their potential involvement in the pathogenesis of AS, and to provide new strategies and targets for the clinical treatment of AS by analyzing the methylation state of H3K27me3 and its interactions with Th17-related factors. Methods: A total of 84 AS patients (42 active AS patiens and 42 patients in the stable phase of AS) were enrolled for the study, while 84 healthy volunteers were enrolled as the controls. Blood samples were collected. Peripheral blood mononuclear cells were isolated. ELISA assay was performed to examine Th17 cells and the relevant cytokines IL-21, IL-22, and IL-17. The mRNA expressions of RORc, JAK2, and STAT3 were analyzed by RT-PCR, the protein expressions of RORc, JAK2/STAT3 pathway protein, H3K27me3 and the relevant protease (EZH2 and JMJD3) were determined by Western blot. Correlation between H3K27me3, EZH2 and JMJD3 and the key signaling pathway molecules of Th cell differentiation was analyzed by Pearson correlation analysis. Results: The mRNA expressions of RORc, JAK2, and STAT3 were significantly higher in the active phase group than those in the stable phase group ( P<0.05). The relative grayscale values of H3K27me3 and EZH2 in the active phase group were lower than those of the stable phase group, which were lower than those of the control group, with the differences being statistically significant ( P<0.05). The relative grayscale values of JMJD3, RORc, JAK2, pJAK2, STAT3, and pSTAT3 proteins were significantly higher in the active phase group than those in the stable phase group, which were higher than those in the control group (all P<0.05). The proportion of Th17 and the expression level of inflammatory factors in the active period group were higher than those in the other two groups (P<0.05). H3K27me3 was negatively correlated with RORc, JAK2, STAT3, and IL-17, JMJD3 was positvely correlated with JAK2, STAT3, and IL-17, and EZH2 was negatively correlated with JAK2, STAT3, and IL-17 (all P<0.05). Conclusion: The low expression of H3K27me3 in AS is influenced by the gene loci JMJD3 and EZH2, which can regulate the differentiation of Th17 cells and thus play a role in the pathogenesis and progression of AS.


Assuntos
Diferenciação Celular , Proteína Potenciadora do Homólogo 2 de Zeste , Epigênese Genética , Histonas , Interleucina-17 , Histona Desmetilases com o Domínio Jumonji , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Fator de Transcrição STAT3 , Espondilite Anquilosante , Células Th17 , Humanos , Espondilite Anquilosante/genética , Espondilite Anquilosante/metabolismo , Células Th17/metabolismo , Células Th17/citologia , Células Th17/imunologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Histonas/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Interleucina-17/metabolismo , Interleucina-17/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Metilação , Interleucinas/metabolismo , Interleucinas/genética , Interleucina 22 , Masculino , Feminino , Adulto
13.
Int Immunopharmacol ; 136: 112305, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38823178

RESUMO

The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.


Assuntos
Interleucinas , Vírus da Doença de Newcastle , Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Vírus da Doença de Newcastle/genética , Vírus da Doença de Newcastle/fisiologia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Vírus Oncolíticos/fisiologia , Humanos , Camundongos , Linhagem Celular Tumoral , Interleucinas/genética , Interleucinas/metabolismo , Neoplasias Hepáticas/terapia , Camundongos Endogâmicos BALB C , Carcinoma Hepatocelular/terapia , Apoptose , Neovascularização Patológica/terapia , Proliferação de Células , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Células Dendríticas/imunologia , Linfócitos T/imunologia
14.
Autoimmunity ; 57(1): 2358070, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38829359

RESUMO

BACKGROUND: Chronic periodontitis (CP) and allergic rhinitis (AR) have attracted wide attention as global public health problems with high incidence. Recent studies have shown that circulating interleukin-27 (IL-27) is associated with the risk of CP and AR. The aim of this study is to analyze the causal effect between them using Mendelian randomization (MR). METHODS: Bidirectional MR analyses were performed with the use of publicly available genome-wide association study (GWAS) data. Summary data on circulating IL-27, CP, and AR published in genome-wide association studies were collected. Instrumental variables (IV) were extracted using assumptions of correlation, independence and exclusivity as criteria. Inverse variance weighting (IVW) was used as the main method, combined with weighted median method (WM) and MR-Egger and other MR Analysis methods for causal inference of exposure and outcome. Cochran's Q and MR-Egger intercept were used for sensitivity analysis. RESULTS: The IVW study showed a causal effect between increased circulating IL-27 levels and increased risk of CP (OR = 1.14, 95%CI = 1.02-1.26, p = .020). Similarly, the increase of circulating IL-27 level had a causal effect on the decreased risk of AR (OR = 0.88, 95%CI = 0.80-0.97, p = .012). In addition, IVW study found that there was a causal between the increased risk of CP and circulating IL-27 level (OR = 1.05, 95%CI = 1.01-1.10, p = .016). However, there was no significant causal relationship between the risk of AR and circulating IL-27 levels (OR = 0.97, 95%CI = 0.91-1.02, p = .209). no significant heterogeneity or horizontal pleiotropy was found in sensitivity analysis. CONCLUSIONS: There is a causal effect between circulating IL-27 level and CP, AR, which will help to find new ideas and methods for the diagnosis and treatment of CP and AR.


Assuntos
Periodontite Crônica , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Rinite Alérgica , Humanos , Rinite Alérgica/genética , Rinite Alérgica/sangue , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , Periodontite Crônica/genética , Periodontite Crônica/sangue , Periodontite Crônica/diagnóstico , Predisposição Genética para Doença , Interleucinas/genética , Interleucinas/sangue , Fatores de Risco , Interleucina-27/sangue , Interleucina-27/genética
15.
Cell Commun Signal ; 22(1): 307, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831315

RESUMO

BACKGROUND: Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24's role in peripheral nociception remain unclear. METHODS: Using patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca2+ channels (T-type channels). RESULTS: IL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2. CONCLUSION: Our findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.


Assuntos
Canais de Cálcio Tipo T , Proteínas Quinases Dependentes de AMP Cíclico , Receptores de Interleucina , Células Receptoras Sensoriais , Transdução de Sinais , Gânglio Trigeminal , Quinases da Família src , Animais , Canais de Cálcio Tipo T/metabolismo , Canais de Cálcio Tipo T/genética , Quinases da Família src/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Gânglio Trigeminal/metabolismo , Masculino , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/fisiologia , Receptores de Interleucina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Interleucinas/metabolismo
16.
Sci Rep ; 14(1): 13133, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849432

RESUMO

The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56highCD16+), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2C+CD57-FcεRIγ+ NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients' bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.


Assuntos
Proliferação de Células , Células Matadoras Naturais , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Humanos , Proliferação de Células/efeitos dos fármacos , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Vacina BCG/imunologia , Vacina BCG/administração & dosagem , Mycobacterium bovis/imunologia , Ativação Linfocitária/efeitos dos fármacos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Interleucinas/metabolismo , Antígeno CD56/metabolismo , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo
17.
Eur Rev Med Pharmacol Sci ; 28(11): 3787-3795, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38884514

RESUMO

OBJECTIVE: Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several chemical mediators occurs. Among them, nerve growth factor (NGF) regulates the inflammatory response related to wound healing and promotes keratinocyte proliferation and angiogenesis. The aim of our study was to investigate the physiological response to injury in children with moderate-severe burns, assaying proNGF, mature NGF (mNGF), interleukins (IL)-1ß, and Il-10 serum levels. PATIENTS AND METHODS: This is a prospective observational study, including twelve children hospitalized for moderate-severe burns at the Gemelli Hospital (Rome). Their laboratory features were compared to those of patients with obstructive hydrocephalus who underwent surgery. RESULTS: Our results showed an increase in proNGF and mNGF serum levels. In burn patients, proNGF levels increased before mNGF, and serum concentrations of both were not correlated with burn extension and depth. The most significant levels of mNGF and proNGF were reported in scalds involving the face. Serum IL-1ß and IL-10 peak levels were reached with a time-course pattern similar to proNGF. CONCLUSIONS: Our preliminary results validate the hypothesis that serum levels of proNGF and mNGF may represent inflammatory biomarkers useful for monitoring burn patients and defining new strategies for their treatment.


Assuntos
Queimaduras , Fator de Crescimento Neural , Humanos , Fator de Crescimento Neural/sangue , Queimaduras/sangue , Criança , Estudos Prospectivos , Feminino , Masculino , Pré-Escolar , Interleucinas/sangue , Interleucina-1beta/sangue , Interleucina-10/sangue , Lactente , Precursores de Proteínas/sangue
18.
Arch Dermatol Res ; 316(7): 349, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850434

RESUMO

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (P < 0.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (P < 0.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (P < 0.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence.


Assuntos
Interleucinas , Micose Fungoide , Neoplasias Cutâneas , Humanos , Micose Fungoide/sangue , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Interleucinas/sangue , Interleucinas/metabolismo , Feminino , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Adulto , Pele/patologia , Pele/metabolismo , Idoso , Biópsia , Biomarcadores Tumorais/sangue
19.
Exp Gerontol ; 193: 112480, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38852656

RESUMO

BACKGROUND: The role of interleukins in sarcopenia development has been acknowledged, yet the specifics of their involvement remain to be fully understood. This study aimed to explore alterations in interleukin levels among sarcopenia patients. METHODS: Searches were conducted in Embase, Medline, and the Cochrane Library for literature published up to May 2023. Eligible observational studies with a diagnosis of sarcopenia were included. The Newcastle-Ottawa Scale was utilized for quality assessment. For data synthesis, a random-effects model was used, and the Mantel-Haenszel method was used for pooled estimates. RESULTS: Of the 7685 articles screened, 37 met the inclusion criteria. Statistically significant differences in the levels of IL-1ß, IL-6 and IL-10 were detected in sarcopenia patients. Specifically, IL-1ß (95 % CI: 0.33 [0.12, 0.54], P < 0.05), IL-6 (95 % CI: 0.91 [0.59, 1.24], P < 0.05), and IL-10 (95 % CI: 0.11 [0.07,0.15], P < 0.05) were detected. However, no significant associations were found between serum IL-4 (95 % CI: 0.36 [-0.18, 0.42], P = 0.44), IL-8 (95 % CI: -1.05 [-3.06, 0.95], P = 0.3), IL-12 (95 % CI: -3.92 [-8.32,0.48], P = 0.08) or IL-17 (95 % CI: 0.22 [-2.43, 2.88], P = 0.87) and sarcopenia. Subgroup analysis showed no significant difference in IL-6 (95 % CI: -0.03 [-0.72, 0.66], P = 0.93) and IL-10 (95 % CI: 0.1 [-0.44, 0.64], P = 0.72) among patients with European standard sarcopenia. CONCLUSIONS: Inflammation plays a role in sarcopenia, and the serum levels of IL-1ß, IL-6, and IL-10 are associated with sarcopenia. Further research is needed to clarify these associations. CLINICAL TRIALS REGISTRATION NUMBER: CRD42024506656.


Assuntos
Interleucinas , Sarcopenia , Idoso , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Interleucinas/sangue , Sarcopenia/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...