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1.
J Chem Ecol ; 45(8): 715-724, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31385154

RESUMO

Plants emit a specific blend of volatiles in response to herbivory and these volatiles, which often attract predators and parasitoids function as an indirect plant defense. The impact of plant volatiles in shaping herbivore defenses is unclear. Here, we report that specific plant volatiles induce immune responses in the polyphagous herbivore, Spodoptera litura. We characterized the hemocyte profile and established their functional significance with respect to ontogeny and exposure to specific plant volatiles. Fifth instar larvae showed the highest number and hemocytes diversity. We characterized seven different types of hemocytes, of which granulocytes performed phagocytosis, oenocytoids showed melanization activity, and plasmatocytes along with granulocytes and oenocytoids were found to be involved in encapsulation. Among the six volatiles tested, exposure to (E)-ß-ocimene caused the highest increase in total hemocytes number (THC) followed by linalool and (Z)-3-hexenyl acetate exposure. Although THC did not differ between these three volatile treatments, circulating hemocytes diversity varied significantly. (E)-ß-ocimene exposure showed higher number of plasmatocytes and phenol oxidase activity. The interaction of the parasitic wasp Bracon brevicornis with (E)-ß-ocimene exposed larvae was poor in terms of delayed paralysis and lower egg deposition. In choice assays, the wasp showed clear preference towards control larvae indicating (E)-ß-ocimene treatment renders the host unattractive. Hemocyte profiles post-parasitoid exposure and (E)-ß-ocimene treatment were similar indicating cue-based priming. When challenged with Bacillus thuringiensis, linalool exposure resulted in the highest survival as compared to other volatiles. Our results show that specific HIPVs can modulate cellular immunity of S. litura, revealing a new role for HIPVs in tri-trophic interactions.


Assuntos
Compostos Orgânicos Voláteis/farmacologia , Vespas/fisiologia , Alcenos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Hemócitos/citologia , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Herbivoria , Interações Hospedeiro-Parasita , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Larva/fisiologia , Monofenol Mono-Oxigenase/metabolismo , Monoterpenos/farmacologia , Oviposição/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Plantas/química , Plantas/metabolismo , Plantas/parasitologia , Compostos Orgânicos Voláteis/química , Vespas/imunologia
2.
Biochem Med (Zagreb) ; 29(3): 030501, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31379458

RESUMO

The complex process of biological aging, as an intrinsic feature of living beings, is the result of genetic and, to a greater extent, environmental factors and time. For many of the changes taking place in the body during aging, three factors are important: inflammation, immune aging and senescence (cellular aging, biological aging). Senescence is an irreversible form of long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress or damage. The purpose of this cell-cycles arrest is to limit the proliferation of damaged cells, to eliminate accumulated harmful factors and to disable potential malignant cell transformation. As the biological age does not have to be in accordance with the chronological age, it is important to find specific hallmarks and biomarkers that could objectively determine the rate of age of a person. These biomarkers might be a valuable measure of physiological, i.e. biological age. Biomarkers should meet several criteria. For example, they have to predict the rate of aging, monitor a basic process that underlies the aging process, be able to be tested repeatedly without harming the person. In addition, biomarkers have to be indicators of biological processes, pathogenic processes or pharmacological responses to therapeutic intervention. It is considered that the telomere length is the weak biomarker (with poor predictive accuracy), and there is currently no reliable biomarker that meets all the necessary criteria.


Assuntos
Envelhecimento , Senescência Celular , Biomarcadores/metabolismo , Dano ao DNA , Humanos , Sistema Imunitário/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Homeostase do Telômero
3.
BMC Bioinformatics ; 20(Suppl 5): 182, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31272390

RESUMO

BACKGROUND: Human immunology studies often rely on the isolation and quantification of cell populations from an input sample based on flow cytometry and related techniques. Such techniques classify cells into populations based on the detection of a pattern of markers. The description of the cell populations targeted in such experiments typically have two complementary components: the description of the cell type targeted (e.g. 'T cells'), and the description of the marker pattern utilized (e.g. CD14-, CD3+). RESULTS: We here describe our attempts to use ontologies to cross-compare cell types and marker patterns (also referred to as gating definitions). We used a large set of such gating definitions and corresponding cell types submitted by different investigators into ImmPort, a central database for immunology studies, to examine the ability to parse gating definitions using terms from the Protein Ontology (PRO) and cell type descriptions, using the Cell Ontology (CL). We then used logical axioms from CL to detect discrepancies between the two. CONCLUSIONS: We suggest adoption of our proposed format for describing gating and cell type definitions to make comparisons easier. We also suggest a number of new terms to describe gating definitions in flow cytometry that are not based on molecular markers captured in PRO, but on forward- and side-scatter of light during data acquisition, which is more appropriate to capture in the Ontology for Biomedical Investigations (OBI). Finally, our approach results in suggestions on what logical axioms and new cell types could be considered for addition to the Cell Ontology.


Assuntos
Ontologias Biológicas , Bases de Dados Factuais , Humanos , Sistema Imunitário/metabolismo , Subunidades Proteicas/metabolismo , Proteínas/metabolismo
4.
Nat Immunol ; 20(7): 783-792, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31213714

RESUMO

Adaptation is the ability of cells, tissues and organisms to rapidly and reversibly modify their properties to maximize fitness in a changing environment. The activity of immune-system components unfolds in the remarkably heterogeneous milieus to which they are exposed in different tissues, during homeostasis or during various acute or chronic pathological states. Therefore, adaptation is essential for immune cells to tune their responses to a large variety of contexts and conditions. The adaptation of immune cells reflects the integration of multiple inputs acting simultaneously or in a temporal sequence, which eventually leads to transcriptional reprogramming and to various functional consequences, some of which extend beyond the duration of the stimulus. A range of adaptive responses have been observed in both adaptive immune cells and innate immune cells; these are referred to with terms such as 'plasticity', 'priming', 'training', 'exhaustion' and 'tolerance', among others, all of which can be useful for defining a certain immunological process or outcome but whose underlying molecular frameworks are often incompletely understood. Here we review and analyze mechanisms of adaptation and memory in immunity with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes.


Assuntos
Adaptação Fisiológica , Imunidade , Memória Imunológica , Imunidade Adaptativa , Animais , Regulação da Expressão Gênica , Histonas/metabolismo , Humanos , Hipersensibilidade/imunologia , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Tolerância Imunológica , Imunidade Inata , Especificidade de Órgãos/imunologia , Fenótipo , Transdução de Sinais
5.
Ther Adv Cardiovasc Dis ; 13: 1753944719851950, 2019 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31144599

RESUMO

Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and mortality in women worldwide. Immune-system activity has been implicated in the etiology of both depression and CVD, but it is unclear how inflammation contributes to sex differences in this comorbidity. This narrative review provides an updated synthesis of research examining the association of inflammation with depression and CVD, and their comorbidity in women. Recent research provides evidence of pro-inflammatory states and sex differences associated with alterations in the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system and the serotonin/kynurenine pathway, that likely contribute to the development of depression and CVD. Changes to inflammatory cytokines in relation to reproductive periods of hormonal fluctuation (i.e. the menstrual cycle, perinatal period and menopause) are highlighted and provide a greater understanding of the unique vulnerability women experience in developing both depressed mood and adverse cardiovascular events. Inflammatory biomarkers hold substantial promise when combined with a patient's reproductive and mental health history to aid in the prediction, identification and treatment of the women most at risk for CVD and depression. However, more research is needed to improve our understanding of the mechanisms underlying inflammation in relation to their comorbidity, and how these findings can be translated to improve women's health.


Assuntos
Doenças Cardiovasculares/imunologia , Depressão/imunologia , Sistema Imunitário/imunologia , Inflamação/imunologia , Reprodução/imunologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Depressão/metabolismo , Depressão/fisiopatologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Cinurenina/imunologia , Cinurenina/metabolismo , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Renina-Angiotensina/imunologia , Serotonina/imunologia , Serotonina/metabolismo , Transdução de Sinais
6.
Medicine (Baltimore) ; 98(19): e15375, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083166

RESUMO

In the study, we tried to evaluate the effects of morphine injected through the systemic or neuraxial route on immune cell function and cytokine production in healthy women.In total, 29 paired samples of fresh peripheral blood were collected from healthy women who had been administered morphine for anesthetic analgesia through intravenous (IV), epidural, or spinal route postpartum. Their isolated peripheral blood mononuclear cells were mitogen-activated and stained with fluorochrome-conjugated anti-CD4, anti-CD8, anti-interleukin (IL)-2, and anti-interferon (IFN)-γ antibodies for flow cytometry, and the plasma levels of cytokines, including IL-6, IFN-α2, IL-10, IL-8, GM-CSF, and monocyte chemoattractant protein (MCP)-1, were measured through enzyme-linked immunosorbent assay.The results demonstrated that regardless of the administration route, morphine delivery slightly reduced IL-2 expression in CD4 cells after activation, and the same effect was not noted for CD8 cells. Intravenous or epidural morphine tended to reduce IFN-γ expression in CD8 cells. Spinal and IV morphine substantially increased IL-6 production, whereas epidural morphine hindered IL-10 and GM-CSF production. IV morphine injection reduced MCP-1 production in plasma. Compared with spinal morphine, IV or epidural morphine may more effectively inhibit the expression of various cytokines and thus affect immune response.All 3 routes of morphine injection tended to decrease IL-2 production by CD4 cells, whereas IV or epidural morphine injection showed lower IFN-γ production by CD8 cells. However, additional large-scale studies with longer follow-up durations are warranted.


Assuntos
Analgésicos Opioides/administração & dosagem , Citocinas/sangue , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Morfina/administração & dosagem , Adulto , Biomarcadores/sangue , Feminino , Humanos , Período Pós-Parto , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
7.
Int J Mol Sci ; 20(9)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035605

RESUMO

Dual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen-activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focus on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSP-mediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR, and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study have the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.


Assuntos
Fosfatases de Especificidade Dupla/metabolismo , Imunomodulação , Proteínas Quinases/metabolismo , Transdução de Sinais , Animais , Evolução Biológica , Células Sanguíneas/metabolismo , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Camundongos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma , Proteômica/métodos
8.
Int J Mol Sci ; 20(9)2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31060234

RESUMO

In recent years, functional interconnections emerged between synaptic transmission, inflammatory/immune mediators, and central nervous system (CNS) (patho)-physiology. Such interconnections rose up to a level that involves synaptic plasticity, both concerning its molecular mechanisms and the clinical outcomes related to its behavioral abnormalities. Within this context, synaptic plasticity, apart from being modulated by classic CNS molecules, is strongly affected by the immune system, and vice versa. This is not surprising, given the common molecular pathways that operate at the cross-road between the CNS and immune system. When searching for a common pathway bridging neuro-immune and synaptic dysregulations, the two major cell-clearing cell clearing systems, namely the ubiquitin proteasome system (UPS) and autophagy, take center stage. In fact, just like is happening for the turnover of key proteins involved in neurotransmitter release, antigen processing within both peripheral and CNS-resident antigen presenting cells is carried out by UPS and autophagy. Recent evidence unravelling the functional cross-talk between the cell-clearing pathways challenged the traditional concept of autophagy and UPS as independent systems. In fact, autophagy and UPS are simultaneously affected in a variety of CNS disorders where synaptic and inflammatory/immune alterations concur. In this review, we discuss the role of autophagy and UPS in bridging synaptic plasticity with neuro-immunity, while posing a special emphasis on their interactions, which may be key to defining the role of immunity in synaptic plasticity in health and disease.


Assuntos
Neuroimunomodulação , Plasticidade Neuronal , Animais , Autofagia , Biomarcadores , Suscetibilidade a Doenças , Metabolismo Energético , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Mediadores da Inflamação/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Transmissão Sináptica
9.
Psychopharmacology (Berl) ; 236(5): 1513-1530, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30982128

RESUMO

Pathological substance use disorders represent a major public health crisis with limited effective treatment options. While much work has been done to understand the neuronal signaling networks and intracellular signaling cascades associated with prolonged drug use, these studies have yielded few successful treatment options for substance use disorders. In recent years, there has been a growing interest to explore interactions between the peripheral immune system, the gut microbiome, and the CNS. In this review, we will present a summary of existing evidence, suggesting a potential role for gut dysbiosis in the pathogenesis of substance use disorders. Clinical evidence of gut dysbiosis in human subjects with substance use disorder and preclinical evidence of gut dysbiosis in animal models of drug addiction are discussed in detail. Additionally, we examine how changes in the gut microbiome and its metabolites may not only be a consequence of substance use disorders but may in fact play a role in mediating behavioral response to drugs of abuse. While much work still needs to be done, understanding the interplay of gut microbiome in substance use disorders may offer a promising avenue for future therapeutic development.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Transtornos Relacionados ao Uso de Substâncias/imunologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Analgésicos Opioides/efeitos adversos , Animais , Disbiose/induzido quimicamente , Disbiose/imunologia , Disbiose/metabolismo , Disbiose/psicologia , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/psicologia
10.
Int J Mol Sci ; 20(7)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959745

RESUMO

Heart failure is a complex clinical syndrome involving a multitude of neurohormonal pathways including the renin-angiotensin-aldosterone system, sympathetic nervous system, and natriuretic peptides system. It is now emerging that neurohumoral mechanisms activated during heart failure, with both preserved and reduced ejection fraction, modulate cells of the immune system. Indeed, these cells express angiotensin I receptors, adrenoceptors, and natriuretic peptides receptors. Ang II modulates macrophage polarization, promoting M2 macrophages phenotype, and this stimulation can influence lymphocytes Th1/Th2 balance. ß-AR activation in monocytes is responsible for inhibition of free oxygen radicals production, and together with α2-AR can modulate TNF-α receptor expression and TNF-α release. In dendritic cells, activation of ß2-AR inhibits IL-12 production, resulting in the inhibition of Th1 and promotion of Th2 differentiation. ANP induces the activation of secretion of superoxide anion in polymorphonucleated cells; reduces TNF-α and nitric oxide secretion in macrophages; and attenuates the exacerbated TH1 responses. BNP in macrophages can stimulate ROS production, up-regulates IL-10, and inhibits IL-12 and TNF-α release by dendritic cells, suggesting an anti-inflammatory cytokines profile induction. Therefore, different neurohormonal-immune cross-talks can determine the phenotype of cardiac remodeling, promoting either favorable or maladaptive responses. This review aims to summarize the available knowledge on neurohormonal modulation of immune responses, providing supportive rational background for further research.


Assuntos
Insuficiência Cardíaca/imunologia , Sistema Imunitário/metabolismo , Neurotransmissores/metabolismo , Animais , Humanos , Imunomodulação , Modelos Biológicos , Pesquisa Médica Translacional
11.
Int J Mol Sci ; 20(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934845

RESUMO

Commensal microbiota contribute to gut homeostasis by inducing transcription of mucosal genes. Analysis of the impact of various microbiota on intestinal tissue provides an important insight into the function of this organ. We used cDNA microarrays to determine the gene expression signature of mucosa isolated from the small intestine and colon of germ-free (GF) mice and animals monoassociated with two E. coli strains. The results were compared to the expression data obtained in conventionally reared (CR) mice. In addition, we analyzed gene expression in colon organoids derived from CR, GF, and monoassociated animals. The analysis revealed that the complete absence of intestinal microbiota mainly affected the mucosal immune system, which was not restored upon monoassociation. The most important expression changes observed in the colon mucosa indicated alterations in adipose tissue and lipid metabolism. In the comparison of differentially expressed genes in the mucosa or organoids obtained from GF and CR mice, only six genes were common for both types of samples. The results show that the increased expression of the angiopoietin-like 4 (Angptl4) gene encoding a secreted regulator of lipid metabolism indicates the GF status.


Assuntos
Perfilação da Expressão Gênica , Vida Livre de Germes/genética , Mucosa Intestinal/metabolismo , Organoides/metabolismo , Animais , Biomarcadores/metabolismo , Colo/metabolismo , Escherichia coli/fisiologia , Regulação da Expressão Gênica , Sistema Imunitário/metabolismo , Imunidade nas Mucosas , Camundongos Endogâmicos BALB C , Microbiota
12.
Int J Mol Sci ; 20(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013709

RESUMO

The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host defense as well as tissue homeostasis. In the event of an insult, the skin-resident immune cells are crucial not only for prevention of infection but also for tissue reconstruction. Deregulation of immune responses often leads to impaired healing and poor tissue restoration and function. In this review, we will discuss the defensive components of the skin and focus on the function of skin-resident immune cells in homeostasis and their role in wound healing.


Assuntos
Sistema Imunitário , Fenômenos Fisiológicos da Pele , Pele/imunologia , Animais , Biomarcadores , Suscetibilidade a Doenças , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Microbiota , Pele/citologia , Pele/inervação , Pele/metabolismo , Cicatrização
13.
Int J Mol Sci ; 20(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013867

RESUMO

The granted European patent EP 2 561 890 describes a procedure for an immunological treatment of cancer. It is based on the principles of the HLA-supported communication of implantation and pregnancy. These principles ensure that the embryo is not rejected by the mother. In pregnancy, the placenta, more specifically the trophoblast, creates an "interface" between the embryo/fetus and the maternal immune system. Trophoblasts do not express the "original" HLA identification of the embryo/fetus (HLA-A to -DQ), but instead show the non-classical HLA groups E, F, and G. During interaction with specific receptors of NK cells (e.g., killer-immunoglobulin-like receptors (KIR)) and lymphocytes (lymphocyte-immunoglobulin-like receptors (LIL-R)), the non-classical HLA groups inhibit these immunocompetent cells outside pregnancy. However, tumors are known to be able to express these non-classical HLA groups and thus make use of an immuno-communication as in pregnancies. If this occurs, the prognosis usually worsens. This patent describes, in a first step, the profiling of the non-classical HLA groups in primary tumor tissue as well as metastases and recurrent tumors. The second step comprises tailored antibody therapies, which is the subject of this patent. In this review, we analyze the underlying mechanisms and describe the currently known differences between HLA-supported communication of implantation and that of tumors.


Assuntos
Imunoterapia , Neoplasias/imunologia , Neoplasias/terapia , Europa (Continente) , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunoterapia/métodos , Neoplasias/genética , Neoplasias/patologia , Evasão Tumoral
14.
Mol Genet Genomics ; 294(3): 679-692, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30834967

RESUMO

Cathartidae is a small family of large-bodied carrion-feeding birds, of which the turkey vulture (Cathartes aura, Cathartidae) is the most widespread distributed. To investigate the chemoreception system, detoxification system, and immune system in the turkey vulture, we compared its genome to 14 other avian genomes. Comparative genomics demonstrated the expansion in the chemoreception system, especially the olfactory receptors, while the genes in the detoxification system of the turkey vulture did not show apparent expansion. We identified five positively selected genes associated with the immune system in the turkey vulture, which was likely to strengthen the immune defense against pathogenic invasion. Functional enrichment analysis indicated that many positively selected genes were involved in the regulation of immune system processes, implying important reorganization of the immune system in the turkey vulture. The turkey vulture-specific missense mutations were found in one positively selected gene (BCL6), and all the missense mutations were classified as deleterious by PolyPhen-2, possibly contributing to immune adaptation to the carrion feeding. Furthermore, we identified four turkey vulture-specific missense mutations in three ß-defensin genes of the turkey vulture, which was an indispensable part in the innate immunity (a natural barrier against invasive microbes including bacteria, fungi, and viruses). Our genomic analyses in the turkey vulture provided insights into the genetic signatures of the adaptation to the carrion feeding.


Assuntos
Proteínas Aviárias/genética , Aves/genética , Genoma/genética , Genômica/métodos , Sequência de Aminoácidos , Animais , Bactérias/patogenicidade , Aves/classificação , Aves/microbiologia , Comportamento Alimentar , Fungos/patogenicidade , Sistema Imunitário/metabolismo , Sistema Imunitário/microbiologia , Filogenia , Homologia de Sequência de Aminoácidos , Virulência , Vírus/patogenicidade , beta-Defensinas/genética
15.
J Neuroinflammation ; 16(1): 64, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894198

RESUMO

BACKGROUND: Orexins (hypocretins, Hcrt) A and B are GPCR-binding hypothalamic neuropeptides known to regulate sleep/wake states and feeding behavior. A few studies have shown that orexin A exhibits anti-inflammatory and neuroprotective properties, suggesting that it might provide therapeutic effects in inflammatory and neurodegenerative diseases like multiple sclerosis (MS). In MS, encephalitogenic Th1 and Th17 cells trigger an inflammatory response in the CNS destroying the myelin sheath. Here, we investigated the effects of peripheral orexin A administration to mice undergoing experimental autoimmune encephalomyelitis (EAE), a widely used model of MS. METHODS: Mice were subcutaneously immunized with myelin oligodendrocyte glycoprotein peptide (MOG)35-55 in CFA. Mice were treated intraperitoneally for five consecutive days with either PBS or 300 µg of orexin A starting at a moderate EAE score. Molecular, cellular, and histological analysis were performed by real-time PCR, ELISA, flow cytometry, and immunofluorescence. RESULTS: Orexin A strongly ameliorated ongoing EAE, limiting the infiltration of pathogenic CD4+ T lymphocytes, and diminishing chemokine (MCP-1/CCL2 and IP-10/CXCL10) and cytokine (IFN-γ (Th1), IL-17 (Th17), TNF-α, IL-10, and TGF-ß) expressions in the CNS. Moreover, orexin A treatment was neuroprotective, decreasing demyelination, astrogliosis, and microglial activation. Despite its strong local therapeutic effects, orexin A did not impair peripheral draining lymph node cell proliferation and Th1/Th17 cytokine production in response to MOG35-55 in vitro. CONCLUSIONS: Peripherally-administered orexin A ameliorated EAE by reducing CNS neuroinflammation. These results suggest that orexins may represent new therapeutic candidates that should be further investigated for MS treatment.


Assuntos
Anti-Inflamatórios/administração & dosagem , Encefalomielite Autoimune Experimental/tratamento farmacológico , Orexinas/administração & dosagem , Animais , Proliferação de Células/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína Básica da Mielina/metabolismo , Glicoproteína Mielina-Oligodendrócito/imunologia , Glicoproteína Mielina-Oligodendrócito/toxicidade , Receptores de Orexina/genética , Receptores de Orexina/metabolismo , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/toxicidade , RNA Mensageiro/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Fatores de Tempo
16.
Chem Biol Interact ; 305: 21-27, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30926318

RESUMO

Voltage-gated potassium (Kv) channels play an essential role in the regulation of membrane excitability and thereby control physiological processes such as cardiac excitability, neural communication, muscle contraction, and hormone secretion. Members of the Kv1 and Kv4 families are known to associate with auxiliary intracellular Kvß subunits, which belong to the aldo-keto reductase superfamily. Electrophysiological studies have shown that these proteins regulate the gating properties of Kv channels. Although the three gene products encoding Kvß proteins are functional enzymes in that they catalyze the nicotinamide adenine dinucleotide phosphate (NAD[P]H)-dependent reduction of a wide range of aldehyde and ketone substrates, the physiological role for these proteins and how each subtype may perform unique roles in coupling membrane excitability with cellular metabolic processes remains unclear. Here, we discuss current knowledge of the enzymatic properties of Kvß proteins from biochemical studies with their described and purported physiological and pathophysiological influences.


Assuntos
Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Aldeídos/metabolismo , Animais , Humanos , Sistema Imunitário/metabolismo , Cetonas/metabolismo , Cinética , Miocárdio/metabolismo , NADP/metabolismo , Sistema Nervoso/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores
17.
Nutrients ; 11(3)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901909

RESUMO

Nutrigenomics studies how environmental factors, such as food intake and lifestyle, influence the expression of the genome. Vitamin D3 represents a master example of nutrigenomics, since via its metabolite 1α,25-dihydroxyvitamin D3, which binds with high-affinity to the vitamin D receptor, the secosteroid directly affects the epigenome and transcriptome at thousands of loci within the human genome. Vitamin D is important for both cellular metabolism and immunity, as it controls calcium homeostasis and modulates the response of the innate and adaptive immune system. At sufficient UV-B exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle often makes the molecule a true vitamin and micronutrient that needs to be taken up by diet or supplementation with pills. The individual's molecular response to vitamin D requires personalized supplementation with vitamin D3, in order to obtain optimized clinical benefits in the prevention of osteoporosis, sarcopenia, autoimmune diseases, and possibly different types of cancer. The importance of endogenous synthesis of vitamin D3 created an evolutionary pressure for reduced skin pigmentation, when, during the past 50,000 years, modern humans migrated from Africa towards Asia and Europe. This review will discuss different aspects of how vitamin D interacts with the human genome, focusing on nutritional epigenomics in context of immune responses. This should lead to a better understanding of the clinical benefits of vitamin D.


Assuntos
Colecalciferol/genética , Genoma Humano/imunologia , Sistema Imunitário/metabolismo , Nutrigenômica , Vitamina D/genética , Epigenômica , Humanos , Transcriptoma
18.
Toxicol Appl Pharmacol ; 366: 96-103, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30703381

RESUMO

Diethyldithiophosphate (DEDTP) is a metabolite produced by the degradation of organophosphorus pesticides and a dialkylphosphate that is chemically synthesized with widespread commercial use. DEDTP is a stable compound, and most studies considered it harmless. However, some studies found adverse effects in vitro, including toxicity in different human cell types. However, there are no in vivo studies characterizing the toxicological effects of DEDTP. Therefore, we investigated the genotoxicity and immunotoxicity of DEDTP in a murine model. We used C57BL/6J and Balb/c mice (6-8-weeks-old) exposed to DEDTP i.p. We established that the medium lethal dose (LD50) of DEDTP was 0.537 g/kg. DEDTP was genotoxic in vivo because it increased the frequency of micronuclei in polychromatic erythrocytes in peripheral blood at 0.05 g/kg. DEDTP showed immunotoxic effects on T and Natural Killer cells and immunomodulatory effects on macrophages, especially M2 type that increased 1000% after 20 days of exposure to 0.01 g/kg. These effects modified the response to a tumoural challenge. DEDTP exposure increased tumour size and reduced the response of lymphocytes to tumoural antigen stimulation. We conclude that exposure to DEDTP produced genotoxic and immunomodulatory effects at environmentally relevant concentrations, which affected the growth of tumours in vivo. These results suggest that DEDTP might reduce the quality of life in exposed individuals, and it exhibits genotoxicity and immunotoxicity despite its stability.


Assuntos
Eritrócitos/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Organotiofosfatos/toxicidade , Praguicidas/toxicidade , Animais , Biomarcadores/sangue , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Eritrócitos/patologia , Feminino , Sistema Imunitário/metabolismo , Sistema Imunitário/patologia , Dose Letal Mediana , Masculino , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Testes para Micronúcleos , Medição de Risco , Fatores de Tempo , Testes de Toxicidade Aguda , Carga Tumoral/efeitos dos fármacos
19.
Artigo em Inglês | MEDLINE | ID: mdl-30711038

RESUMO

Several reports have shown the positive effects of ß-glucans on the immune. Howeverthese studies have a broad experimental design including ß-glucans compounds. Consequently, a study using the same ß-glucan molecule, administration route and experimental design is needed to compare the effects of ß-glucan across vertebrate species. For this end, during 28 days we fed four different vertebrate species: mice, dogs, piglets and chicks, with two ß-glucan molecules (BG01 and BG02). We measured the serum interleukin 2 as an indicator of innate immune response, the neutrophils and monocytes phagocytosis index as a cellular response and antibody formation as an adaptive response. The results clearly showed that the different ß-glucan molecules exhibited biologically differently behaviors, but both molecules stimulate the immune system in a similar pattern in these four species. This finding suggests that vertebrates shared similar mechanisms/patterns in recognizing the ß-glucans and confirms the benefits of ß-glucans across different vertebrate species.


Assuntos
Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , beta-Glucanas/metabolismo , Imunidade Adaptativa , Ração Animal , Animais , Suplementos Nutricionais , Cães , Feminino , Imunidade Inata , Masculino , Camundongos , Fagocitose/imunologia , Suínos , Vertebrados
20.
Mol Immunol ; 108: 75-80, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30784765

RESUMO

RNA polymerase II (Pol II) binds to promoter-proximal regions of inducible target genes that are controlled and not transcribed by several negative elongation factors, which is known as Pol II stalling. The occurrence of stalling is due to particular modification signatures and structural conformations of chromatin that affect Pol II elongation. The existence and physiological importance of Pol II stalling implies that there is a dynamic balance in chromatin regulation prior to endogenous or exogenous stimulation. In this review, we discuss the effects of ATP-dependent chromatin remodeling complexes and histone modification via transcriptional machinery Pol II C-terminal domain phosphorylated at serine 5 (S5P RNAPII) initiation and S2P RNAPII elongation on the expression or silence of specific genes after the production of activated or differentiated signals or cytokines. The response occurs immediately during immune cell development and function, and it also includes the generation of immunological memories. This summary suggests that the host immune response genes involve a novel mechanism of selectively regulatory chromatin remodeling, a fundamental and crucial aspect of epigenetic regulation.


Assuntos
Montagem e Desmontagem da Cromatina , Sistema Imunitário/metabolismo , RNA Polimerase II/metabolismo , Animais , Humanos , Memória Imunológica , Inflamação/genética , Transcrição Genética
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