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نتیجه جستجو - Cytokines

تعداد مقالات یافته شده: 13
ردیف عنوان نوع
1 Infection during childhood and the risk of violent criminal behavior in adulthood
عفونت درطی دوران کودکی و خطر رفتارهای جنایتکارانه در بزرگسالی-2020
Infections during brain development appear to contribute to cognitive impairment and aggressive behavior, as well as to a number of developmental mental disorders closely associated with violent criminal behavior. Yet, no study has thus far ever investigated whether infections during brain development increases the risk of violent criminality later in life. In this population-based cohort study, about 2.2 million individuals born in Sweden between the years 1973 and 1995 were included in an effort to estimate the association between infections during childhood (registered ICD-10 diagnoses of infections incurred before the age of 14 years) and violent criminal behavior (registered convictions for a violent crime between the ages of 15 and 38 years, prior to December 31, 2011). After inclusion of several sociodemographic parameters, risks of violent criminal behavior conferred by childhood infections – expressed as hazard ratios (HRs) and 95% confidence intervals (CIs) – were calculated by means of Cox regression. Mediation analyses were performed to explore the effect of psychiatric disorders on the association between infections during childhood and violent criminality. Results revealed a modest, yet significant, association between an infection during childhood and violent criminality later in life (adjusted HR 1.14, 95% CI 1.12–1.16). Infections during the first year of life and infections in the central nervous system were associated with the highest risks of subsequent violent criminality (adjusted HR 1.20, 95% CI 1.18–1.23, and adjusted HR 1.17, 95% CI 1.08–1.26, respectively). The association was partly mediated by the presence of a psychiatric disorder. In summary, independent of a wide range of covariates, our results suggest that infections during brain development could be part of the genesis of violent criminal behavior.
Keywords: Criminality | Violence | Psychiatric disorder | Cytokines | Immune response
مقاله انگلیسی
2 Biochanin A: A novel bioactive multifunctional compound from nature
Biochanin A: رویکرد ترکیب چند منظوره زیست فعال طبیعت-2020
Natural products (NPs) will continue to serve humans asmatchless source of novel drug leads and an inspiration for the synthesis of non-natural drugs. As our scientific understanding of ‘nature’ is rapidly expanding, itwould be worthwhile to illuminate the pharmacological distinctions of NPs to the scientific community and the public. Flavonoids have long fascinated scientists with their remarkable structural diversity as well as biological functions. Consequently, this review aims to shed light on the sources and pharmacological significance of a dietary isoflavone, biochanin A, which has been recently emerged as a multitargeted and multifunctional guardian of human health. Biochanin A possesses anti-inflammatory, anticancer, neuroprotective, antioxidant, anti-microbial, and hepatoprotective properties. It combats cancer development by inducing apoptosis, inhibition of metastasis and arresting cell cycle via targeting several deregulated signaling pathways of cancer. It fights inflammation by blocking the expression and activity of pro-inflammatory cytokines via modulation of NF-κB and MAPKs. Biochanin A acts as a neuroprotective agent by inhibiting microglial activation and apoptosis of neurons. As biochanin A has potential to modulate several biological networks, thus, it can be anticipated that this therapeutically potent compound might serve as a novel lead for drug development in the near future.
Keywords: Biochanin A | Isoflavone | Anticancer | Anti-inflammatory | Antioxidant | Neuroprotective | Anti-microbial
مقاله انگلیسی
3 Immunostimulatory activity of Y-shaped DNA nanostructures mediated through the activation of TLR9
فعالیت ایمنی تحریک کننده نانوساختارهای واسطه DNA شکل-Y از طریق فعال سازی TLR9-2019
Immunostimulatory oligodeoxynucleotides (DNAs) have been widely studied in pharmaceutical and biomedical research fields for applications in cancer immunotherapy and vaccination. Toll-like receptors (TLRs) are critical for the instruction and orchestration of the host immune system composed of innate and adaptive immunity. In particular, TLR9 responds to DNAs with unmethylated deoxycytosine-deoxyguanosine (CpG) motifs, thereby inducing the activation of innate immune cells, such as dendritic cells, and consequently, adaptive immune cells. In this study, we developed two kinds of Y-shaped double-stranded DNA nanostructures (Y-DNAs), including a single unit composed of three DNA strands (YS-DNA) and a ligated multiunit complex formed by crosslinking each YS-DNA (YL-DNA), and investigated whether they have immunostimulatory activity in innate immune cells. YS-DNA and YL-DNA induced the production of immune cytokines such as IL-12 and TNF-α and the expression of costimulatory molecules such as CD80 and CD86 in primary mouse dendritic cells and macrophage cells (RAW264.7 cells). A Coprecipitation study demonstrated that YL-DNA was directly associated with TLR9. The induction of immune cytokines by YS-DNA and YL-DNA was abolished in TLR9-deficient primary mouse dendritic cells. The results demonstrated that Y-DNAs induced the activation of dendritic cells and macrophages mediated by the activation of TLR9, as shown by the expression of immune cytokines and costimulatory molecules. The results suggest that Y-DNA nanostructures provide a beneficial strategy for immunotherapy by modulating the immune system.
Keywords: Immunostimulatory DNA | Pattern recognition receptor | Nanostructures | Toll-like receptor
مقاله انگلیسی
4 Innate immunity as the trigger of systemic autoimmune diseases
ایمنی ذاتی به عنوان محرک بیماریهای خود ایمنی سیستماتیک-2019
The innate immune system consists of a variety of elements controlling and participating in virtually all aspects of inflammation and immunity. It is crucial for host defense, but on the other hand its improper activation is also thought to be responsible for the generation of autoimmunity and therefore diseases such as autoimmune arthritides like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS) or inflammatory bowel disease. The innate immune system stands both at the beginning as well as the end of autoimmunity. On one hand, it regulates the activation of the adaptive immune system and the breach of selftolerance, as antigen presenting cells (APCs), especially dendritic cells, are essential for the activation of naïve antigen specific T cells, a crucial step in the development of autoimmunity. Various factors controlling the function of dendritic cells have been identified that directly regulate lymphocyte homeostasis and in some instances the generation of organ specific autoimmunity. Moreover, microbial cues have been identified that are prerequisites for the generation of several specific autoimmune diseases. On the other hand, the innate immune system is also responsible for mediating the resulting organ damage underlying the clinical symptoms of a given autoimmune disease via production of proinflammatory cytokines that amplify local inflammation and further activate other immune or parenchymal cells in the vicinity, the generation of matrix degrading and proteolytic enzymes or reactive oxygen species directly causing tissue damage. In the last decades, molecular characterization of cell types and their subsets as well as both positive and negative regulators of immunity has led to the generation of various scenarios of how autoimmunity develops, which eventually might lead to the development of targeted interventions for autoimmune diseases. In this review, we try to summarize the elements that are contributing to the initiation and perpetuation of autoimmune responses.
Keywords: Innate immunity | Autoimmunity | Dendritic cells | Pattern recognition receptors | Microbiome in autoimmunity
مقاله انگلیسی
5 The three-dimensional structure and recognition mechanism of Manduca sexta peptidoglycan recognition protein-1
ساختار و مکانیسم شناختی سه بعدی از شناسایی پروتئین 1 پپتیدوگلیکان ماندوکا sexta-2019
Peptidoglycan recognition proteins (PGRPs) recognize bacteria through their unique cell wall constituent, peptidoglycans (PGs). PGRPs are conserved from insects to mammals and all function in antibacterial defense. In the tobacco hornworm Manduca sexta, PGRP1 and microbe binding protein (MBP) interact with PGs and hemolymph protease-14 precursor (proHP14) to yield active HP14. HP14 triggers a serine protease network that produces active phenoloxidase (PO), Spätzle, and other cytokines to stimulate immune responses. PGRP1 binds preferentially to diaminopimelic acid (DAP)-PGs of Gram-negative bacteria and Gram-positive Bacillus and Clostridium species than Lys-PGs of other Gram-positive bacteria. In this study, we synthesized DAP- and Lysmuramyl pentapeptide (MPP) and monitored their associations with M. sexta PGRP1 by surface plasmon resonance. The Kd values (0.57 μM for DAP-MPP and 45.6 μM for Lys-MPP) agree with the differential recognition of DAP- and Lys-PGs. To reveal its structural basis, we produced the PGRP1 in insect cells and determined its structure at a resolution of 2.1 Å. The protein adopts a fold similar to those from other PGRPs with a classical Lshaped PG-binding groove. A unique loop lining the shallow groove suggests a different ligand-binding mechanism. In summary, this study provided new insights into the PG recognition by PGRPs, a critical first step that initiates the serine protease cascade
Keywords: Insect immunity | Pattern recognition | Hemolymph protein | Serine protease | Prophenoloxidase activation | Melanization
مقاله انگلیسی
6 Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors
مونوسیت های بیماران مبتلا به آنژین بی ثبات میزان بالایی از گیرنده های کموکاین و تشخیص الگو-2019
Background and aims: Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). Methods: Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. Results: Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. Conclusions: Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.
Keywords: Atherosclerosis | Monocytes subsets | Heat shock protein 60 | Intermediate monocytes
مقاله انگلیسی
7 Persistence of Integrase-Deficient Lentiviral Vectors Correlates with the Induction of STING-Independent CD8+ T Cell Responses
Persistence of Integrase-Deficient Lentiviral Vectors Correlates with the Induction of STING-Independent CD8+ T Cell Responses-2019
Lentiviruses are among the most promising viral vectors for in vivo gene delivery. To overcome the risk of insertional mutagenesis, integrase-deficient lentiviral vectors (IDLVs) have been developed. We show here that strong and persistent specific cytotoxic T cell (CTL) responses are induced by IDLVs, which persist several months after a single injection. These responses were associated with the induction of mild and transient maturation of dendritic cells (DCs) and with the production of low levels of inflammatory cytokines and chemokines. They were independent of the IFN-I, TLR/MyD88, interferon regulatory factor (IRF), retinoic acid induced gene I (RIG-I), and stimulator of interferon genes (STING) pathways but require NF-kB signaling in CD11c+ DCs. Despite the lack of integration of IDLVs, the transgene persists for 3 months in the spleen and liver of IDLV-injected mice. These results demonstrate that the capacity of IDLVs to trigger persistent adaptive responses is mediated by a weak and transient innate response, along with the persistence of the vector in tissues
مقاله انگلیسی
8 Role of peptide transporter 2 and MAPK signaling pathways in the innate immune response induced by bacterial peptides in alveolar epithelial cells
نقش حمل و نقل پپتید 2 و مسیرهای سیگنالینگ MAPK در پاسخ ایمنی ذاتی ناشی از پپتیدهای باکتریایی در سلولهای اپیتلیال آلوئول-2019
Aims: The innate immune response induced by bacterial peptidoglycan peptides, such as γ-D-glutamyl-mesodiaminopimelic acid (iE-DAP), is an important host defense system. However, little is known about the innate immune response in the lung alveolar region. In this study, we examined induction of the innate immune response by iE-DAP in human alveolar epithelial cell lines, NCI-H441 (H441) and A549. Main methods: Induction of the innate immune response was evaluated by measuring the mRNA expression of cytokines and their release into the culture medium. Key findings: iE-DAP treatment increased the mRNA expression of interleukin (IL)-6 and IL-8, and increased release of these pro-inflammatory cytokines into the culture medium in H441 cells, but not in A549 cells. Lack of release of these cytokines in A549 cells may have been due to lack of peptide transporter 2 (PEPT2) function. Intracellular nucleotide-binding oligomerization domain 1 (NOD1) recognizes iE-DAP and activates downstream signaling pathways to initiate the immune response. Therefore, the role of mitogen-activated protein kinase (MAPK) signaling pathways was examined in H441 cells. As a result of inhibition studies, receptor-interacting serine/threonine-protein kinase 2 and MAPK signaling pathways, such as p38 MAPK and extracellular signalregulated kinase, but not c-Jun N-terminal kinase, were determined to be involved in the innate immune response in H441 cells. In addition, the nuclear factor κB pathway also played a role in the innate immune response. Significance: These findings indicated that the innate immune response induced by bacterial peptides could occur in a PEPT2- and NOD1-dependent manner in alveolar epithelial cells.
Keywords: Alveolar epithelial cells | Bacterial peptides | Innate immune response| Mitogen-activated protein kinase | Pattern recognition receptor | Peptide transporter 2
مقاله انگلیسی
9 Neuronal transcriptomic responses to Japanese encephalitis virus infection with a special focus on chemokine CXCL11 and pattern recognition receptors RIG-1 and MDA5
پاسخهای رونویسی عصبی به عفونت ویروس آنسفالیت ژاپنی با تمرکز ویژه روی کموکاین CXCL11 و گیرنده های تشخیص الگوی RIG-1 و MDA5-2019
Japanese encephalitis virus (JEV) causes central nervous system neuronal injury and inflammation. A clear understanding of neuronal responses to JEV infection remains elusive. Using the Affymetrix array to investigate the transcriptome of infected SK-N-MC cells, 1316 and 2737 dysregulated genes (≥ 2/−2 fold change, P < 0.05) were found at 48 hours post-infection (hpi) and 60 hpi, respectively. The genes were mainly involved in anti-microbial responses, cell signalling, cellular function and maintenance, and cell death and survival. Among the most highly upregulated genes (≥ 10 folds, P < 0.05) were chemokines CCL5, CXCL11, IL8 and CXCL10. The upregulation and expression of CXCL11 were confirmed by qRT-PCR and immunofluorescence. Pathogen recognition receptors retinoic acid-inducible gene-1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA5) were also upregulated. Our results strongly suggest that neuronal cells play a significant role in immunity against JEV. CXCL11, RIG-1 and MDA5 and other cytokines may be important in neuropathogenesis.
Keywords: Japanese encephalitis virus | Transcriptome | RNA microarray | Proinflammatory mediators | Neuronal infection | CXCL11 | RIG-1 | MDA5
مقاله انگلیسی
10 Structural characterization and immunomodulatory activity of a novel acid polysaccharide isolated from the pulp of Rosa laevigata Michx fruit
خصوصیات ساختاری و فعالیت سیستم ایمنی از پلی ساکارید اسید جدید جدا شده از خمیر میوه Rosa laevigata Michx-2019
A novel acid polysaccharide (PPRLMF-2) with the Mw of 137,123 Da and a triple-helix conformation was first isolated from the pulp of Rosa laevigata Michx fruit. Structural characterization showed that PPRLMF- 2 consisted of rhamnose (7.6%), arabinose (26.5%), xylose (3.5%), mannose (0.9%), glucose (5.7%), galactose (31.9%) and galacturonic acid (23.9%). The methylation and NMR (1D and 2D) analysis revealed that PPRLMF-2 contained 16 types of glycosidic linkages. The immunomodulatory activity assays indicated that PPRLMF-2 could significantly enhance phagocytosis, the secretion and mRNA expression of cytokines in RAW 264.7 cells. Additionally, SR, GR, TLR-2, and TLR-4 were the main pattern recognition receptors (PRRs) of PPRLMF-2 to upregulate the p-ERK, p-JNK, p-p38, and p-p65. These results suggested that PPRLMF-2 could recognize the PRRs of the macrophages to enhance the immunomodulatory activity via activation of the MAPKs and NF-jB signaling pathways. This study provides important implications of PPRLMF-2 as an attractive immunomodulatory functional food.
Keywords: Rosa laevigata Michx | Polysaccharide | Structural characterization | RAW264.7 cells | Immunomodulatory activity
مقاله انگلیسی
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