Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.097
Filtrar
1.
Orthopade ; 48(11): 911-916, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31531702

RESUMO

Inflammatory rheumatic diseases are often associated with secondary osteoporosis, as many inflammatory messengers can interfere with bone metabolism and adversely affect it. In addition to a decrease in densitometric bone density, remodeling occurs in the trabecular bone, which can lead to a disturbed microarchitecture and increase the risk of fracture.Central to this is the close integration of bone metabolism and the immune system. Proinflammatory cytokines play an important role not only in the inflammatory process, but also as mediators of bone resorption because they stimulate osteoclastogenesis and induce further signal transduction cascades with negative influence on the bone. The understanding gained in recent years of the underlying immunological processes has led to the development of new and targeted treatment approaches.


Assuntos
Reabsorção Óssea/imunologia , Citocinas/fisiologia , Osteoporose , Doenças Reumáticas/imunologia , Remodelação Óssea , Reabsorção Óssea/metabolismo , Humanos , Mediadores da Inflamação/fisiologia , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Doenças Reumáticas/metabolismo
2.
Adv Exp Med Biol ; 1165: 381-406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399975

RESUMO

Renal inflammation is the initial, healthy response to renal injury. However, prolonged inflammation promotes the fibrosis process, which leads to chronic pathology and eventually end-stage kidney disease. There are two major sources of inflammatory cells: first, bone marrow-derived leukocytes that include neutrophils, macrophages, fibrocytes and mast cells, and second, locally activated kidney cells such as mesangial cells, podocytes, tubular epithelial cells, endothelial cells and fibroblasts. These activated cells produce many profibrotic cytokines and growth factors that cause accumulation and activation of myofibroblasts, and enhance the production of the extracellular matrix. In particular, activated macrophages are key mediators that drive acute inflammation into chronic kidney disease. They produce large amounts of profibrotic factors and modify the microenvironment via a paracrine effect, and they also transdifferentiate to myofibroblasts directly, although the origin of myofibroblasts in the fibrosing kidney remains controversial. Collectively, understanding inflammatory cell functions and mechanisms during renal fibrosis is paramount to improving diagnosis and treatment of chronic kidney disease.


Assuntos
Mediadores da Inflamação/fisiologia , Nefropatias/fisiopatologia , Rim/patologia , Transdiferenciação Celular , Fibrose , Humanos , Leucócitos/citologia , Macrófagos/citologia , Miofibroblastos/citologia
3.
Adv Exp Med Biol ; 1127: 181-194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31140179

RESUMO

Despite the progress made over the last decades to understand the mechanisms underlying tissue damage and neurological deficits after neurotrauma, there are currently no effective treatments in the clinic. It is well accepted that the inflammatory response in the CNS after injury exacerbates tissue loss and functional impairments. Unfortunately, the use of potent anti-inflammatory drugs, such as methylprednisolone, fails to promote therapeutic recovery and also gives rise to several undesirable side effects related to immunosuppression. The injury-induced inflammatory response is complex, and understanding the mechanisms that regulate this inflammation is therefore crucial in the quest to develop effective treatments. Bioactive lipids have emerged as potent molecules in controlling the initiation, coordination, and resolution of inflammation and in promoting tissue repair and recovery of homeostasis. These bioactive lipids are produced by cells involved in the inflammatory response, and their defective synthesis leads to persistent chronic inflammation, tissue damage, and fibrosis. The present chapter discusses recent evidence for the role of some of these bioactive lipids, in particular, eicosanoid and pro-resolving lipid mediators, in the regulation of inflammation after neurotrauma and highlights the therapeutic potential of some of these lipids in enhancing neurological outcomes after CNS injuries.


Assuntos
Mediadores da Inflamação/fisiologia , Inflamação , Lipídeos/fisiologia , Traumatismos do Sistema Nervoso , Eicosanoides/fisiologia , Humanos
4.
J Affect Disord ; 250: 249-259, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30870775

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a complex and heterogeneous disorder in which clinical symptoms can widely differ among patients. Neurovegetative symptoms, i.e. decreased or increased appetite, changes in body weight and sleep disturbances, described as 'melancholic' or 'atypical' features of a depressive episode, are the most variable symptoms among patients with MDD. We hypothesized biomarkers differences underlying this neurovegetative variability in major depression. METHODS: We systematically reviewed, according to the PRISMA guidelines, the role of specific metabolic, hormonal and inflammatory biomarkers in drug-free MDD patients, that could have neurobiological effects on appetite, weight regulation and circadian rhythms, influencing eating behaviour and sleep patterns. All studies regarding the co-occurrence of disturbed sleep and appetite were examined. RESULTS: Besides the well-known leptin and ghrelin, other biomarkers such as BDNF, VEGF, NPY, orexin, and the recent discovered nesfatin-1 seem to be involved in neurovegetative changes in depressive disorders playing a role in the regulation of affective states, stress reactions and sleep patterns. Interestingly, based on the existing evidence, ghrelin, orexin and nesfatin-1 could be linked both to sleep and appetite regulation in depressed patients. LIMITATIONS: Heterogeneous studies with low sample size. CONCLUSIONS: Despite the wide heterogeneity of results, studies on biomarkers of appetite and sleep in MDD are an interesting field of research to explain the neurobiological substrates of depressive symptoms that deserve further investigation.


Assuntos
Apetite/fisiologia , Biomarcadores/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Metabolismo Energético/fisiologia , Hormônios/fisiologia , Mediadores da Inflamação/fisiologia , Sono/fisiologia , Transtorno Depressivo Maior/psicologia , Humanos
5.
Yakugaku Zasshi ; 138(11): 1329-1334, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30381640

RESUMO

Impaired insulin signaling in adipose tissue and skeletal muscle causes insulin resistance associated with the development of type 2 diabetes. However, the molecular mechanisms underlying insulin resistance remain to be elucidated. In this review, we describe the current understanding of the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and tumor necrosis factor (TNF)-α on insulin signal transduction in adipocytes. First, we determined that atorvastatin inhibits the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 through a decrease in the RhoA-Rho-kinase pathway, resulting in the inhibition of glucose uptake. Second, we found that TNF-α induces IRS-1 phosphorylation at serine residues 636/639 and inhibits the tyrosine phosphorylation of IRS-1 through the increase in both extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation. Interestingly, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside, an AMP-activated protein kinase activator, suppresses TNF-α-induced IRS-1 serine phosphorylation at 636/639 and the phosphorylation of ERK by enhancing interactions between ERK and dual-specificity phosphatase-9. These results may be helpful in understanding the mechanisms underlying insulin resistance.


Assuntos
Atorvastatina/efeitos adversos , Diabetes Mellitus/etiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Mediadores da Inflamação/fisiologia , Resistência à Insulina , Insulina/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Proteínas Quinases Ativadas por AMP/fisiologia , Adipócitos/metabolismo , Animais , Fosfatases de Especificidade Dupla/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Serina/metabolismo , Tirosina/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
6.
Reprod Biol Endocrinol ; 16(1): 45, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743077

RESUMO

BACKGROUND: Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. OBJECTIVE: To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. METHODS: PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. RESULTS: The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. CONCLUSION: There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.


Assuntos
Doenças do Sistema Endócrino/complicações , Sistema Hipotálamo-Hipofisário/fisiopatologia , Infertilidade Feminina/etiologia , Inflamação/complicações , Obesidade/complicações , Ovário/fisiopatologia , Animais , Doenças do Sistema Endócrino/fisiopatologia , Feminino , Hormônios/metabolismo , Hormônios/fisiologia , Humanos , Infertilidade Feminina/fisiopatologia , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/fisiologia , Obesidade/fisiopatologia , Reprodução/fisiologia
7.
J Eur Acad Dermatol Venereol ; 32 Suppl 1: 1-15, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29533490

RESUMO

Atopic dermatitis (AD) is a common, highly pruritic, chronic inflammatory skin disease. Dysfunction of the epidermal barrier is witnessed by an increased transepidermal water loss in lesional and non-lesional AD skin. The inflammation in lesional AD skin is well characterized. Non-lesional skin of AD patients shows histological signs of a subclinical inflammation and a pro-inflammatory cytokine milieu. This microinflammation is present even in seemingly healed skin and must be taken into account regarding treatment of AD. Emollients provide a safe and effective method of skin barrier improvement, because they provide the skin with a source of exogenous lipids, thus improving its barrier function. The use of emollients is recommended for all AD patients irrespective of overall disease severity. Patients with moderate to severe AD should combine the emollients with a proactive therapy regimen of topical calcineurin inhibitors or topical corticosteroids. Skin areas affected by active eczema in flare should receive daily anti-inflammatory therapy first before introducing emollients, to induce rapid relief of skin lesions and pruritus. The microinflammation persisting in seemingly healed AD lesions should be addressed by a proactive treatment approach, consisting of minimal anti-inflammatory therapy and liberal, daily use of emollients. An emollient containing an extract of Rhealba oat plantlet has shown anti-inflammatory and barrier repairing properties, and was clinically tested in studies targeting the microinflammation in AD. All emollients based on Rhealba oat plantlet extract are free of oat protein, as the Rhealba extract is derived from the aerial parts of the oat plantlet and is unrelated to oatmeal proteins. The Rhealba oat plantlet extract is produced in a specific process, allowing the extraction of high levels of active principles such as flavonoids and saponins, whilst being virtually free of oat proteins to minimize the risk for allergic reactions.


Assuntos
Avena/química , Dermatite Atópica/tratamento farmacológico , Emolientes/uso terapêutico , Inflamação/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Proteínas de Plantas/análise , Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Citocinas/fisiologia , Dermatite Atópica/patologia , Dermatite Atópica/fisiopatologia , Dermatite Atópica/prevenção & controle , Humanos , Mediadores da Inflamação/fisiologia , Cicatrização
9.
J Vasc Surg Venous Lymphat Disord ; 6(3): 358-366, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29439934

RESUMO

OBJECTIVE: Chronic venous insufficiency (CVI) affects 25 million adults in the United States. Little emphasis has been placed on inflammatory changes associated with CVI. We hypothesize that in patients with early to mid-stage benign varicose vein disease, differences in circulating inflammatory mediators will be manifested in blood draining the involved area vs circulating blood in control subjects. METHODS: Patients undergoing either endovenous ablation or sclerotherapy for Clinical, Etiology, Anatomy, and Pathophysiology clinical class 3 to 5 disease underwent phlebotomy from regional veins at the time of the procedure. The patient's age, gender, clinical class, duration of symptoms, presence of superficial truncal reflux by duplex ultrasound, and treatment modality were recorded. Plasma from patients and banked blood samples from healthy volunteers (HVs) were subjected to Luminex (EMD Millipore, Billerica, Mass) to evaluate the expression of an established panel of 20 inflammatory mediators. Mediator concentrations were compared between patients and HVs using Mann-Whitney U tests. Importantly, computational analysis allowed us to compare not only the panel of inflammatory mediators but also the inflammatory networks connecting these mediators to one another. Principal components were analyzed to assess network robustness in each group. RESULTS: CVI venous blood revealed significantly lower levels of monokine induced by γ interferon, soluble interleukin (IL) 2 receptor α chain, IL-4, IL-6, IL-7, tumor necrosis factor α, eotaxin, and granulocyte-macrophage colony-stimulating factor than blood from controls. Inflammatory networks were significantly less complex and less robust in the CVI patients compared with HVs. Based on principal component analysis, responses among HVs were more varied than those of CVI patients. CONCLUSIONS: We demonstrate that patients with CVI have significant differences not only in blood-borne inflammatory mediators but also in the interconnectedness of these mediators with one another and in their principal inflammatory characteristics. Results suggest hypoinflammation in chronic nonhealing changes in CVI. These novel findings, if validated in larger cohorts, may help predict the risk of disease progression or response to therapy in the future and may guide mechanistic studies on tissue responses to CVI.


Assuntos
Mediadores da Inflamação/fisiologia , Insuficiência Venosa/fisiopatologia , Adulto , Biomarcadores/sangue , Coleta de Amostras Sanguíneas/métodos , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Componente Principal , Estudos Prospectivos , Transdução de Sinais/fisiologia , Insuficiência Venosa/sangue , Insuficiência Venosa/etiologia
10.
PLoS One ; 13(2): e0192824, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29438401

RESUMO

Metabolic disorders due to over-nutrition are a major global health problem, often associated with obesity and related morbidities. Obesity is peculiar to humans, as it is associated with lifestyle and diet, and so difficult to reproduce in animal models. Here we describe a model of human central adiposity based on a 3-tissue system consisting of a series of interconnected fluidic modules. Given the causal link between obesity and systemic inflammation, we focused primarily on pro-inflammatory markers, examining the similarities and differences between the 3-tissue model and evidence from human studies in the literature. When challenged with high levels of adiposity, the in-vitro system manifests cardiovascular stress through expression of E-selectin and von Willebrand factor as well as systemic inflammation (expressing IL-6 and MCP-1) as observed in humans. Interestingly, most of the responses are dependent on the synergic interaction between adiposity and the presence of multiple tissue types. The set-up has the potential to reduce animal experiments in obesity research and may help unravel specific cellular mechanisms which underlie tissue response to nutritional overload.


Assuntos
Inflamação/fisiopatologia , Modelos Biológicos , Obesidade Abdominal/fisiopatologia , Vasculite/fisiopatologia , Adiposidade , Albuminas/biossíntese , Animais , Biomarcadores/metabolismo , Reatores Biológicos , Técnicas de Cocultura/métodos , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Inflamação/complicações , Mediadores da Inflamação/fisiologia , Gordura Intra-Abdominal/fisiopatologia , Dispositivos Lab-On-A-Chip , Lipídeos/biossíntese , Obesidade Abdominal/complicações , Vasculite/complicações
11.
PLoS One ; 13(2): e0192333, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29408929

RESUMO

Painful neuropathy (PN) is a prevalent condition in patients with metabolic syndrome (MetS). However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN) remain unclear. In the current study, high-fat-fed mice (HF mice) were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF) mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, and interleukin (IL)-6, IL-1ß as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG) of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.


Assuntos
Citocinas/fisiologia , Mediadores da Inflamação/fisiologia , Síndrome Metabólica/fisiopatologia , Dor/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Animais , Dieta Hiperlipídica , Hipercolesterolemia/fisiopatologia , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Ganho de Peso
12.
Eye (Lond) ; 32(3): 491-505, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29171506

RESUMO

Inflammasomes, key molecular regulators that play an important role in inflammation, consist of a central protein, an adaptor protein ASC (apoptosis speck-like protein) and a caspase-1 protein. Upon activation, caspase-1 induces maturation of cytokines such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). The release of these cytokines can result in inflammation. Inflammasomes are activated by a variety of factors and their activation involves complex signalling leading to resolution of infection, but can also contribute to the pathology of inflammatory, autoimmune, and infectious diseases. The role of NLRP1, NLRP3, NLRC4 and AIM2 inflammasomes in the pathogenesis of ocular diseases such as glaucoma, age related macular degeneration (AMD), diabetic retinopathy, dry eye and infections of the eye has been established over the past decade. In experimental studies and models, inhibition of inflammasomes generally helps to reduce the inflammation associated with these eye diseases, but as yet the role of these inflammasomes in many human eye diseases is unknown. Therefore, a need exists to study and understand various aspects of inflammasomes and their contribution to the pathology of human eye diseases. The goal of this review is to discuss the role of inflammasomes in the pathology of eye diseases, scope for anti-inflammasome therapy, and current research gaps in inflammasome-related eye disease.


Assuntos
Oftalmopatias/etiologia , Inflamassomos/antagonistas & inibidores , Inflamassomos/fisiologia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/fisiologia , Inflamação/metabolismo , Oftalmopatias/imunologia , Oftalmopatias/metabolismo , Humanos , Imunidade Inata/imunologia , Inflamação/etiologia , Serpinas/uso terapêutico , Proteínas Virais/uso terapêutico
13.
Nihon Rinsho Meneki Gakkai Kaishi ; 40(5): 367-376, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29238019

RESUMO

  Osteoclasts are differentiated from precursors of the monocyte/macrophage lineage originated from bone marrow hematopoietic stem cells and are the sole bone-resorbing cells in the body. Osteoclast differentiation is thought to require M-CSF (macrophage colony-stimulating factor) and RANKL (receptor activator of nuclear factor kappa-B ligand) signaling. However, it has recently been proposed that under chronic inflammatory conditions, such as systemic autoimmune diseases (e.g., rheumatoid arthritis), an increase in inflammatory cytokine levels within joints induces pathological osteoclast differentiation, causing excessive bone resorption. In addition, the authors have reported that stimulating mouse bone marrow monocytes and human CD14+ monocytes with combination of TNFα and IL-6 can induce differentiation of osteoclast-like cells, which are cells with bone resorption activity. In the present article, we discuss the mechanism of osteoclast differentiation of RANKL-independent bone-resorbing cells, using both data from the aforementioned report as well as the latest findings. Understanding the mechanisms underlying RANKL-independent, cytokine-mediated osteoclast differentiation could facilitate the development of novel therapies for inflammatory joint diseases.


Assuntos
Diferenciação Celular/genética , Inflamação/etiologia , Inflamação/patologia , Osteoclastos/citologia , Osteoclastos/fisiologia , Animais , Artrite Reumatoide/etiologia , Artrite Reumatoide/patologia , Reabsorção Óssea/etiologia , Citocinas/fisiologia , Descoberta de Drogas , Humanos , Mediadores da Inflamação/fisiologia , Interleucina-6/fisiologia , Fator Estimulador de Colônias de Macrófagos , Camundongos , Terapia de Alvo Molecular , Osteoclastos/patologia , Ligante RANK/fisiologia , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/fisiologia
14.
Cancer Res ; 77(24): 7094-7108, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29051178

RESUMO

Toll-like receptors (TLR) are conserved immune sensors mediating antimicrobial and antitumoral responses, but recent evidence implicates them in promoting carcinogenesis in certain cancers. Kaposi sarcoma is caused by infection of Kaposi sarcoma-associated herpesvirus (KSHV) and is characterized by uncontrolled neoangiogenesis and inflammation. Here, we show that TLR4 is upregulated in KSHV-infected spindle tumor cells in human Kaposi sarcoma lesions. In a model of KSHV-induced cellular transformation, KSHV upregulated expression of TLR4, its adaptor MyD88, and coreceptors CD14 and MD2. KSHV induction of TLR4 was mediated by multiple viral miRNAs. Importantly, the TLR4 pathway was activated constitutively in KSHV-transformed cells, resulting in chronic induction of IL6, IL1ß, and IL18. Accordingly, IL6 mediated constitutive activation of the STAT3 pathway, an essential event for uncontrolled cellular proliferation and transformation. TLR4 stimulation with lipopolysaccharides or live bacteria enhanced tumorigenesis while TLR4 antagonist CLI095 inhibited it. These results highlight an essential role of the TLR4 pathway and chronic inflammation in KSHV-induced tumorigenesis, which helps explain why HIV-infected patients, who frequently suffer from opportunistic bacterial infections and metabolic complications, frequently develop Kaposi sarcoma. Cancer Res; 77(24); 7094-108. ©2017 AACR.


Assuntos
Transformação Celular Viral/genética , Herpesvirus Humano 8/fisiologia , Inflamação/complicações , Sarcoma de Kaposi/genética , Receptor 4 Toll-Like/fisiologia , Animais , Carcinogênese/genética , Proliferação de Células/genética , Células Cultivadas , Feminino , Humanos , Inflamação/genética , Mediadores da Inflamação/fisiologia , Camundongos , Camundongos Nus , Ratos , Fator de Transcrição STAT3/metabolismo , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologia , Transdução de Sinais/genética
15.
Clín. investig. arterioscler. (Ed. impr.) ; 29(5): 224-230, sept.-oct. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-166868

RESUMO

La aterosclerosis, una conocida enfermedad arterial prevalente, ocasiona el deterioro progresivo de los vasos afectados provocando reducción del flujo sanguíneo con diversas complicaciones, y los síntomas suelen manifestarse en estadios avanzados de la enfermedad. En este sentido, las clásicas alternativas terapéuticas resultan insuficientes debido al carácter muchas veces irreversible del daño provocado. Por lo tanto, emerge la necesidad de implementar novedosas formas más eficaces para administrar fármacos y también el desarrollo de nuevas dianas terapéuticas que reduzcan la progresión de la lesión aterosclerótica. Además, resulta de especial interés la implementación de nuevas herramientas para la prevención, diagnóstico y tratamiento de esta patología cardiovascular, focalizando la atención en lograr un mejor control sobre el sistema inmunológico. En esta revisión se pone en relieve el conocimiento actual sobre la nanotecnología como una alternativa terapéutica potencial, moderna y prometedora, aplicada a la patología aterosclerótica, pero se advierte también sobre posibles complicaciones de su uso (AU)


Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion. The implementation of new tools for prevention, diagnosis and treatment of this cardiovascular disease is of special interest, focusing our attention on achieving a more effective control of the immune system. Finally, this review highlights the latest knowledge about nanotechnology as a powerful, modern, and promising therapeutic alternative applied to atherosclerotic disease, as well as warning of the potential complications with their use (AU)


Assuntos
Humanos , Nanotecnologia/tendências , Aterosclerose/terapia , Placa Aterosclerótica/fisiopatologia , Progressão da Doença , Mediadores da Inflamação/fisiologia , Inflamação/fisiopatologia , Ativação de Macrófagos/fisiologia , Hipercolesterolemia/fisiopatologia
16.
Rheumatology (Oxford) ; 56(10): 1804-1813, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957555

RESUMO

Objective: miRNAs are small, signal-strand, non-coding RNAs that function in post-transcriptional regulation. We analysed the in vivo effect of miR-106b (miR-106b-5p) on inflammatory bone loss in CIA mice. Methods: CIA mice are developed by injecting DAB/1 mice with bovine type II collagen containing Freund's adjuvant and then the in vivo effect of miR-106b is examined. On day 22, mice were given lentiviral negative control, lentiviral-mediated miR-106b mimics or lentiviral-mediated miR-106b inhibitor via orbital injection on a weekly basis. Morphological changes in the ankle joints were assessed via micro-CT and histopathology and cytokine expression levels were examined via immunohistochemical staining, ELISA or flow cytometric analysis. miR-106b and osteoclastic-related gene expression was evaluated via quantitative real-time PCR. Results: CIA mice were found to have increased miR-106b expression and CIA-associated bone loss and inflammatory infiltration. miR-106b inhibitor treatment markedly decreased arthritis incidence and attenuated bone destruction and histological severity compared with the control group. Moreover, miR-106b inhibitor treatment suppressed RANK ligand (RANKL) expression, increased osteoprotegerin (OPG) expression and reduced the RANKL:OPG ratio in CIA mice. miR-106b inhibition also significantly decreased inflammatory mediator production in joint sections and reduced serum pro-inflammatory cytokine levels when compared with the control group. Additionally, miR-106b inhibition decreased tartrate-resistant acid phosphatase-positive cell numbers and suppressed murine bone marrow macrophage differentiation. Conclusion: These findings indicate that miR-106b inhibition can ameliorate CIA-associated inflammation and bone destruction and thus may serve as a potential therapeutic for human RA treatment.


Assuntos
Artrite Experimental/genética , Osso e Ossos/patologia , Regulação para Baixo , Articulações/patologia , MicroRNAs/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Osso e Ossos/metabolismo , Colágeno Tipo II , Citocinas/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/fisiologia , Articulações/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , MicroRNAs/antagonistas & inibidores , Osteoclastos/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
17.
Am J Chin Med ; 45(6): 1253-1271, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28830206

RESUMO

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of severe sepsis or septic shock. In this study, we examined the effects of SFN on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. The anti-inflammatory activities of SFN were monitored based on its effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of SFN were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice. SFN inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. SFN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with SFN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in vivo. Our results indicate that SFN is a possible therapeutic agent that can be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.


Assuntos
Anti-Inflamatórios , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/fisiologia , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/fisiologia , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Fitoterapia , Sepse/tratamento farmacológico , Sepse/genética , Transdução de Sinais/efeitos dos fármacos , Animais , Brassicaceae/química , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Proteína HMGB1/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Leucócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
J Cardiovasc Pharmacol ; 70(2): 61-73, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28763371

RESUMO

Proinflammatory reaction by the body occurs acutely in response to injury that is considered primarily beneficial. However, sustained proinflammatory cytokines observed with chronic pathologies such as metabolic syndrome, cancer, and arthritis are detrimental and in many cases is a major cardiovascular risk factor. Proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor α (TNFα) have long been implicated in cardiovascular risk and considered to be a major underlying cause for heart failure (HF). The failure of the anti-TNFα therapy for HF indicates our elusive understanding on the dichotomous role of proinflammatory cytokines on acutely beneficial effects versus long-term deleterious effects. Despite these well-described observations, less is known about the mechanistic underpinnings of proinflammatory cytokines especially TNFα in pathogenesis of HF. Increasing evidence suggests the existence of an active cross-talk between the TNFα receptor signaling and G-protein-coupled receptors such as ß-adrenergic receptor (ßAR). Given that ßARs are the key regulators of cardiac function, the review will discuss the current state of understanding on the role of proinflammatory cytokine TNFα in regulating ßAR function.


Assuntos
Citocinas/fisiologia , Mediadores da Inflamação/fisiologia , Receptores Acoplados a Proteínas-G/fisiologia , Animais , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Transdução de Sinais/fisiologia
19.
Neurochem Res ; 42(11): 3199-3219, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28786048

RESUMO

Sepsis-associated encephalopathy (SAE) is related to cognitive sequelae in patients in the intensive care unit and can have serious impacts on quality of life after recovery. Although various pathogenic pathways are involved in SAE development, little is known concerning the global role of long non-coding RNAs (lncRNAs) in SAE. Herein, we employed transcriptome sequencing approaches to characterize the effects of lipopolysaccharide (LPS) on lncRNA expression patterns in brain tissue isolated from Sprague-Dawley rats with and without SAE. We performed high-throughput transcriptome sequencing after LPS was intraperitoneally injected and predicted targets and functions using bioinformatics tools. Subsequently, we explored the results in detail according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. LncRNAs were differentially expressed in brain tissue after LPS treatment. After 6 h of LPS exposure, expression of 400 lncRNAs were significantly changed, including an increase in 316 lncRNAs and a decrease in 84 lncRNAs. In addition, 155 mRNAs were differentially expressed, with 84 up-regulated and 71 down-regulated. At 24 h post-treatment, expression of 117 lncRNAs and 57 mRNAs was consistently elevated, while expression of 79 lncRNAs and 21 mRNAs was decreased (change >1.5-fold; p <0.05). We demonstrated for the first time that differentially expressed lncRNAs were predicted to be enriched in a post-chaperonin tubulin folding pathway (GO: 007023), which is closely related to the key step in the tubulin folding process. Interestingly, the predicted pathway (KEGG 04360: axon guidance) was significantly changed under the same conditions. These results reveal that LPS might influence the construction and polarization of microtubules, which exert predominant roles in synaptogenesis and related biofunctions in the rodent central nervous system (CNS). An inventory of LPS-modulated expression profiles from the rodent CNS is an important step toward understanding the function of mRNAs, including lncRNAs, and suggests that microtubule malformation and dysfunction may be involved in SAE pathogenesis.


Assuntos
Perfilação da Expressão Gênica/métodos , Mediadores da Inflamação/fisiologia , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Encefalopatia Associada a Sepse/genética , Animais , Expressão Gênica , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , RNA Longo não Codificante/biossíntese , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Encefalopatia Associada a Sepse/metabolismo
20.
Epilepsia ; 58 Suppl 3: 39-47, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28675559

RESUMO

Animal models have provided a wealth of information on mechanisms of epileptogenesis and comorbidogenesis, and have significantly advanced our ability to investigate the potential of new therapies. Processes implicating brain inflammation have been increasingly observed in epilepsy research. Herein we discuss the progress on animal models of epilepsy and comorbidities that inform us on the potential role of inflammation in epileptogenesis and comorbidity pathogenesis in rodent models of West syndrome and the Theiler's murine encephalomyelitis virus (TMEV) mouse model of viral encephalitis-induced epilepsy. Rat models of infantile spasms were generated in rat pups after right intracerebral injections of proinflammatory compounds (lipopolysaccharides with or without doxorubicin, or cytokines) and were longitudinally monitored for epileptic spasms and neurodevelopmental and cognitive deficits. Anti-inflammatory treatments were tested after the onset of spasms. The TMEV mouse model was induced with intracerebral administration of TMEV and prospective monitoring for handling-induced seizures or seizure susceptibility, as well as long-term evaluations of behavioral comorbidities of epilepsy. Inflammatory processes are evident in both models and are implicated in the pathogenesis of the observed seizures and comorbidities. A common feature of these models, based on the data so far available, is their pharmacoresistant profile. The presented data support the role of inflammatory pathways in epileptogenesis and comorbidities in two distinct epilepsy models. Pharmacoresistance is a common feature of both inflammation-based models. Utilization of these models may facilitate the identification of age-specific, syndrome- or etiology-specific therapies for the epilepsies and attendant comorbidities, including the drug-resistant forms.


Assuntos
Infecções por Cardiovirus/imunologia , Modelos Animais de Doenças , Epilepsia/imunologia , Inflamação Neurogênica/tratamento farmacológico , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/imunologia , Theilovirus , Pesquisa Médica Translacional , Animais , Anticonvulsivantes/uso terapêutico , Descoberta de Drogas , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/imunologia , Epilepsia/tratamento farmacológico , Humanos , Lactente , Mediadores da Inflamação/fisiologia , Camundongos , Inflamação Neurogênica/imunologia , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA