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1.
J Biomed Sci ; 26(1): 85, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647037

RESUMO

INTRODUCTION: Efficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics. METHODS: In this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems. RESULTS: In this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only. CONCLUSIONS: Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Camptotecina/administração & dosagem , Celulose/administração & dosagem , Ciclodextrinas/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Nanopartículas/administração & dosagem , Animais , Camundongos , Organismos Livres de Patógenos Específicos
2.
Int J Mol Sci ; 20(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614433

RESUMO

Alterations on the immune system caused by omega-3 fatty acids have been described for 30 years. This family of polyunsaturated fatty acids exerts major alterations on the activation of cells from both the innate and the adaptive immune system, although the mechanisms for such regulation are diverse. First, as a constitutive part of the cellular membrane, omega-3 fatty acids can regulate cellular membrane properties, such as membrane fluidity or complex assembly in lipid rafts. In recent years, however, a new role for omega-3 fatty acids and their derivatives as signaling molecules has emerged. In this review, we describe the latest findings describing the effects of omega-3 fatty acids on different cells from the immune system and their possible molecular mechanisms.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Ácidos Graxos Ômega-3/efeitos adversos , Imunidade Inata/efeitos dos fármacos , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Humanos , Fluidez de Membrana/efeitos dos fármacos , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/metabolismo
3.
Mol Cell ; 76(1): 110-125.e9, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31474573

RESUMO

Failure to make adaptive immune responses is a hallmark of aging. Reduced B cell function leads to poor vaccination efficacy and a high prevalence of infections in the elderly. Here we show that reduced autophagy is a central molecular mechanism underlying immune senescence. Autophagy levels are specifically reduced in mature lymphocytes, leading to compromised memory B cell responses in old individuals. Spermidine, an endogenous polyamine metabolite, induces autophagy in vivo and rejuvenates memory B cell responses. Mechanistically, spermidine post-translationally modifies the translation factor eIF5A, which is essential for the synthesis of the autophagy transcription factor TFEB. Spermidine is depleted in the elderly, leading to reduced TFEB expression and autophagy. Spermidine supplementation restored this pathway and improved the responses of old human B cells. Taken together, our results reveal an unexpected autophagy regulatory mechanism mediated by eIF5A at the translational level, which can be harnessed to reverse immune senescence in humans.


Assuntos
Autofagia/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Senescência Celular/efeitos dos fármacos , Imunossenescência/efeitos dos fármacos , Fatores de Iniciação de Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Espermidina/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Fatores Etários , Envelhecimento , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/deficiência , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Células HEK293 , Humanos , Memória Imunológica/efeitos dos fármacos , Células Jurkat , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células NIH 3T3 , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais
4.
Emerg Microbes Infect ; 8(1): 1168-1177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379262

RESUMO

Mannose-capped lipoarabinomannan (ManLAM) is a high molecular mass amphipathic lipoglycan identified in pathogenic Mycobacterium tuberculosis (M. tb) and M. bovis Bacillus Calmette-Guérin (BCG). ManLAM, serves as both an immunogen and a modulator of the host immune system, and its critical role in mycobacterial survival during infection has been well-characterized. ManLAM can be recognized by various types of receptors on both innate and adaptive immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer T (NKT) cells, T cells and B cells. MamLAM has been shown to affect phagocytosis, cytokine production, antigen presentation, T cell activation and polarization, as well as antibody production. Exploring the mechanisms underlying the roles of ManLAM during mycobacterial infection will aid in improving tuberculosis (TB) prevention, diagnosis and treatment interventions. In this review, we highlight the interaction between ManLAM and receptors, intracellular signalling pathways triggered by ManLAM and its roles in both innate and adaptive immune responses.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/análise , Lipopolissacarídeos/análise , Manose/análise , Mycobacterium bovis/química , Mycobacterium tuberculosis/química , Animais , Humanos , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Receptores Imunológicos/agonistas , Transdução de Sinais
5.
Immunopharmacol Immunotoxicol ; 41(4): 513-520, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31397191

RESUMO

Exposure to environmentally relevant doses of arsenic has several harmful effects on the human immune system. In traditional Eastern medicines, nettle has been used as an anti-inflammatory agent to treat rheumatism and osteoarthritis. Fumaric acid (FA) as a major effective compound in nettle was chosen based on very accurate virtual screening to find antagonist for TLR4/MD structure. In this study, the in vitro therapeutic effects of FA on arsenic-exposed monocytes-derived dendritic cells (MDDCs) were evaluated. All the canonical functions of dendritic cells in bridging innate and adaptive immune system including phagocytosis and antigen-presenting capacity, and also cytokines secretion, were evaluated after exposure to arsenic/FA. FA profoundly over-expressed antigen-presenting capacity of MDDCs after exposure to arsenic through the upregulation of MHCιι. However, phagocytosis capacity of arsenic-exposed MDDCs is not compensated for, by treatment with FA. Arsenic up-regulates pro-inflammatory cytokines independents of TLR4 pathway. FA surprisingly mitigates the up-regulation of IL-1ß and TNF-α but not TLR4 and NF-kB. Moreover, FA increases the viability of MDDCs even at a high dose of arsenic. Totally, FA reduced inflammatory factors induced by arsenic. This finding confirmed that nettle and other medicinal plants containing similar structures with FA could be further analyzed as valuable candidates for the reduction of drastic effects of arsenic in human immune systems.


Assuntos
Arsênico/farmacologia , Células Dendríticas/efeitos dos fármacos , Fumaratos/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Monócitos/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Imunidade Adaptativa/efeitos dos fármacos , Adulto , Apresentação do Antígeno/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação/metabolismo , Masculino , Monócitos/metabolismo , Fagocitose/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
6.
Curr Pharm Biotechnol ; 20(15): 1236-1243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333121

RESUMO

BACKGROUND: The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. CONCLUSION: Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.


Assuntos
Adjuvantes Imunológicos/farmacologia , Lectinas/farmacologia , Plantas/química , Polifenóis/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Adjuvantes Imunológicos/isolamento & purificação , Animais , Antígenos/imunologia , Citocinas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Lectinas/imunologia , Lectinas/isolamento & purificação , Polifenóis/imunologia , Polifenóis/isolamento & purificação , Vacinação/métodos , Vacinas/imunologia
7.
Fish Shellfish Immunol ; 92: 913-924, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306761

RESUMO

A feeding trial was performed to compare the effects of five ethanol herbal extracts (bhumi amla, Phyllanthus amarus Schum and Thonn [Pa]; guava, Psidium guajava L. [Pg]; sensitive plant, Mimosa pudica L. [Mp]; neem, Azadirachta indica A. Juss [Ai] and asthma plant, Euphorbia hirta L. [Eh]) on the immune response and disease resistance against Edwardsiella ictaluri infection of striped catfish (Pangasianodon hypophthalmus). Fish were fed diets supplemented with two doses of each plant extract (0% [basal diet], 0.4% Eh [Eh0.4], 2.0% Eh [Eh2.0], 0.2% Pa [Pa0.2], 1.0% Pa [Pa1.0], 0.2% Pg [Pg0.2], 1.0% Pg [Pg1.0], 0.4% Mp [Mp0.4], 2.0% Mp [Mp2.0], 0.4% Ai [Ai0.4], 2.0% Ai [Ai2.0]) for 8 weeks. Results showed that hematological parameters (total red blood cells, white blood cells, lymphocytes, monocytes, and neutrophils) of fish fed extract-based diets were significantly higher than in those fed the control diet (p < 0.05) after 4 and 8 weeks. Plasma lysozyme activity increased in fish whose diets contained both doses of Eh (p < 0.05) in week 4 (W4), whereas lysozyme activity increased in fish fed 0.2% Pa and Pg, and 2.0% Ai and Eh (p < 0.05) in week 8 (W8). The lysozyme levels in skin mucus did not significantly differ between treatments (p > 0.05) in W4 and after the bacterial challenge test. At the end of the feeding trial, levels of ACH50 significantly increased in most of extract groups compared to the control group (p < 0.05). Total immunoglobulin increased considerably in both the plasma and skin mucus of fish fed extract-supplemented diets after 8 weeks. In addition, dietary supplementation with Pg, Mp, Pa0.2, Eh2.0, and Ai0.4 for 8 weeks considerably reduced the cumulative mortality against E. ictaluri infection in striped catfish. The results suggest that plant extracts possibly modulate the striped catfish immune response in a time and dose dependent manner. Specifically, diets enriched with extracts of P. guajava at 0.2 and 1.0%, or M. pudica at 2.0% for 8 weeks, have great potential for improving striped catfish health by enhancing the immune system and reducing mortality against bacterial challenges.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Peixes-Gato/imunologia , Resistência à Doença/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Extratos Vegetais/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Edwardsiella ictaluri/fisiologia , Infecções por Enterobacteriaceae/imunologia , Doenças dos Peixes/imunologia , Extratos Vegetais/administração & dosagem , Distribuição Aleatória
8.
Int Immunopharmacol ; 73: 552-559, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177081

RESUMO

Zerumbone exhibited various biological properties including in vitro immunosuppressive effects. However, its modulatory activity on the immune responses in experimental animal model is largely unknown. This investigation was conducted to explore the effects of daily treatment of zerumbone (25, 50, and 100 mg/kg) isolated from Zingiber zerumbet rhizomes for 14 days on various cellular and humoral immune responses in Balb/C mice. For measurement of adaptive immunity, sheep red blood cells (sRBC) were used to immunize the mice on day 0 and orally fed with similar doses of zerumbone for 14 days. The effects of zerumbone on phagocytosis, nitric oxide (NO) release, myeloperoxidase (MPO) activity, proliferation of T and B cells, lymphocyte phenotyping, cytokines release in serum by activated T cells, delayed type hypersensitivity (DTH) and immunoglobulins production (IgG and IgM) were investigated. Zerumbone downregulated the engulfment of E. coli by peritoneal macrophages and the release of NO and MPO in a concentration-dependent manner. Zerumbone showed significant and concentration-dependent suppression of T and B lymphocytes proliferation and inhibition of the Th1 and Th2 cytokines release. At higher concentrations of zerumbone, the % expression of CD4+ and CD8+ in splenocytes was significantly inhibited. Zerumbone also concentration-dependently demonstrated strong suppression on sRBC-triggered swelling of mice paw in DTH. Substantial suppression of anti-sRBC immunoglobulins antibody titer was noted in immunized and zerumbone-treated mice in a concentration-dependent manner. The potent suppressive effects of zerumbone on the immune responses suggest that zerumbone can be a potential candidate for development of immunosuppressive agent.


Assuntos
Imunossupressores/farmacologia , Sesquiterpenos/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Linfócitos B/efeitos dos fármacos , Citocinas/metabolismo , Eritrócitos/imunologia , Escherichia coli , Imunidade Humoral/efeitos dos fármacos , Imunoglobulinas/imunologia , Masculino , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Fagocitose/efeitos dos fármacos , Ovinos , Baço/citologia , Linfócitos T/efeitos dos fármacos , Zingiberaceae
9.
Cancer Immunol Immunother ; 68(7): 1073-1085, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161238

RESUMO

Cryptotanshinone (CT), a purified compound initially isolated from the dried roots of Salvia militorrhiza. Bunge, exhibits cytotoxic antitumor effects on many tumors. We have shown that CT possesses the dual capacities to concomitantly inhibit the proliferation of lung cancer cells and promote the generation of antitumor immunity. In this study, we investigated whether CT could be used to treat hepatocellular carcinoma (HCC) using a mouse Hepa1-6 model. CT inhibited the proliferation of mouse hepatoma (Hepa1-6) cells in vitro by inducing Hepa1-6 cells apoptosis through the JAK2/STAT3 signaling pathway. In addition, CT activated macrophages and polarized mouse bone marrow-derived macrophages (BMM) toward an M1 phenotype in vitro, which depended on the TLR7/MyD88/NF-κB signaling pathway. Furthermore, CT significantly inhibited the growth of syngeneic Hepa1-6 hepatoma tumors, and, in combination with anti-PD-L1 cured Hepa1-6-bearing mice with the induction of long-term anti-Hepa1-6 specific immunity. Immunoprofiling of treated Hepa1-6-bearing mice revealed that CT-promoted activation of tumor-infiltrating macrophages and dendritic cells, induction of antitumor T cell response, and infiltration of effector/memory CD8 T cells in the tumor tissue. Importantly, the immunotherapeutic effects of CT and anti-PD-L1 depended on the presence of CD8 T cells. Thus, CT and anti-PD-L1 may provide an effective immunotherapeutic regimen for human HCC based on a combination of cytotoxic effects and induction of tumor-specific immunity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Fenantrenos/farmacologia , Receptor 7 Toll-Like/metabolismo , Imunidade Adaptativa/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Ativação Linfocitária , Macrófagos/imunologia , Macrófagos/metabolismo , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fenantrenos/uso terapêutico , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos , Receptor 7 Toll-Like/imunologia , Resultado do Tratamento
10.
Expert Opin Drug Metab Toxicol ; 15(7): 565-575, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31211608

RESUMO

Introduction: There are concerns that opioids may be associated with an increased risk of infection. This safety issue is alarming given the widespread use of opioids in pain management. Areas covered: In this review, we summarize the pharmacologic aspects of opioids related to the immune system and to the assumed pathophysiology of opioid-related infections. We also synthesize and critically appraise the available clinical evidence on the potential association between the use of opioids and the risk of infection. PubMed was searched from inception to 1 February 2019 for all articles published in English with terms corresponding to 'opioids' and 'infections'. Expert opinion: Morphine appears to suppress the immune system via affecting cells of the innate and the adaptive immunity as well as via modulating the hypothalamic-pituitary-adrenal axis. However, knowledge gaps exist regarding the immune-related pharmacology of non-morphine opioids. Observational studies have suggested an increased risk of infections associated with the use of opioids. However, methodological limitations such as confounding by indication due to the choice of non-use as comparator render the interpretation of most of these studies difficult. Thus, further efforts in preclinical research and well-conducted observational studies are needed to provide more robust evidence in this regard.


Assuntos
Analgésicos Opioides/efeitos adversos , Sistema Imunitário/efeitos dos fármacos , /etiologia , Imunidade Adaptativa/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Animais , Humanos , Imunidade Inata/efeitos dos fármacos , /imunologia , Morfina/administração & dosagem , Morfina/efeitos adversos , Dor/tratamento farmacológico , Risco
11.
Drug Des Devel Ther ; 13: 1421-1436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118577

RESUMO

Background: 3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP), a novel synthetic curcumin analogue has been revealed to possess strong in vitro and in vivo immunosuppressive effects. Purpose: The aim of present study was to prepare and characterize BBP-encapsulated polylactic-co-glycolic acid-block-polyethylene glycol (PLGA-b-PEG) nanoparticles and to evaluate its in vivo efficacy against innate and adaptive immune responses. Methods: Male BALB/c mice were orally administered with BBP alone and BBP- encapsulated nanoparticles equivalent to 5, 10 and 20 mg/kg of BBP in distilled water for a period of 14 days. The immunomodulatory potential was appraised by determining its effects on non-specific and specific immune parameters. Results: The results showed that BBP was successfully encapsulated in PLGA-b-PEG polymer with 154.3 nm size and high encapsulation efficiency (79%) while providing a sustained release for 48 hours. BBP nanoparticles showed significant enhanced dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity, reactive oxygen species (ROS) production, serum levels of ceruloplasmin and lysozyme, immunoglobulins and myloperoxidase (MPO) plasma levels when compared to unencapsulated BBP. Enhanced dose-dependent inhibition was also observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines, and reduction in rat paw oedema in BBP nanoparticles treated mice. At higher doses the suppressive effects of the BBP nanoparticles on various cellular and humoral parameters of immune responses were comparable to that of cyclosporine-A at 20 mg/kg. Conclusion: These findings suggest that the immunosuppressive effects of BBP were enhanced as PLGA-b-PEG nanoparticles.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Curcumina/análogos & derivados , Imunidade Inata/efeitos dos fármacos , Imunossupressores/farmacologia , Nanopartículas/química , Piperidinas/farmacologia , Polietilenoglicóis/química , Poliglactina 910/química , Imunidade Adaptativa/imunologia , Animais , Curcumina/síntese química , Curcumina/química , Curcumina/farmacologia , Relação Dose-Resposta a Droga , Imunidade Inata/imunologia , Imunossupressores/síntese química , Imunossupressores/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Piperidinas/síntese química , Piperidinas/química , Ovinos , Relação Estrutura-Atividade
12.
Science ; 364(6442)2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31123109

RESUMO

Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Asma/terapia , Glicoproteínas/química , Glicoproteínas/farmacologia , Imunidade Inata/efeitos dos fármacos , Lisofosfolipase/química , Lisofosfolipase/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Asma/imunologia , Asma/patologia , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/terapia , Cristalização , Modelos Animais de Doenças , Glicoproteínas/administração & dosagem , Glicoproteínas/imunologia , Células Caliciformes/imunologia , Células Caliciformes/patologia , Humanos , Epitopos Imunodominantes/imunologia , Imunoglobulina E/imunologia , Lisofosfolipase/administração & dosagem , Lisofosfolipase/imunologia , Metaplasia , Camundongos , Camundongos Endogâmicos C57BL , Muco/imunologia
13.
Immunopharmacol Immunotoxicol ; 41(1): 150-162, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31038378

RESUMO

Objective: Recently, many researches with different viewpoints have focused on application of immunotherapy agents in treatment of spinal cord injury (SCI) according to neuroprotective results in some neurodegenerative disease. Glatiramer acetate (GA) is the most commonly used drug for Multiple sclerosis (MS) patients that exerts an immunomodulatory effect against Myelin basic protein (MBP) antigen. Materials and methods: High-dose (2mg/kg) treatment of GA for 28 consecutive days after SCI was compared with its low-dose (0.5 mg/kg) treatment, SCI control and Sham control rat groups. Results: High-dose GA group had significantly worsened outcome in standard functional recovery evaluation test (BBB) 12 weeks after SCI compared to SCI control and low-dose GA groups, which was confirmed by augmented spinal cavity volume and reduced ventral horn motor neurons in high-dose GA group; however, there was no significant difference between low-dose GA and control SCI group. In addition, proliferation test performed on lymphocytes from spleen and lymph nodes one week after SCI showed that high-dose GA injection has more significant effect on Division Index (DI) in response to MBP stimulation compared to low-dose GA and control SCI groups, which was associated with significant increase in IFN-γ, IL-4, and IL-17A secretion. Conclusion: Along with confirmation of deleterious aspects of autoimmunity resulting from autoreactive lymphocytes against myelin antigens in SCI, this study has shown that high-dose immunotherapy using GA, especially in acute phase after SCI, overwhelms any neuroprotective effect of adoptive immune system.


Assuntos
Reação de Fase Aguda/tratamento farmacológico , Acetato de Glatiramer/administração & dosagem , Imunoterapia/métodos , Proteína Básica da Mielina/imunologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Reação de Fase Aguda/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Acetato de Glatiramer/uso terapêutico , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/imunologia , Traumatismos da Medula Espinal/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
14.
Microbiol Immunol ; 63(7): 269-279, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31141221

RESUMO

Pseudorabies, a herpesvirus infection, is mainly controlled by using attenuated live vaccines. In this study, the effect of ginseng stem and leaf saponins (GSLS) in combination with selenium (Se; in the form of sodium selenite) on vaccination against attenuated pseudorabies virus (aPrV) was evaluated. It was found that GSLS and Se have an adjuvant effect and that a combination of GSLS and Se stimulates significantly enhanced immune responses than does GSLS or Se alone. Following oral administration of GSLS, mice immunized with an attenuated PrV vaccine diluted in Se-containing physiological saline solution (PSS) provoked a significantly stronger gB-specific serum antibodies response (IgG, IgG1 and IgG2a), enhanced lymphocyte proliferation and cytolytic activity of NK cells, along with higher production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) by splenocytes. Notably, the combination of GSLS and Se conferred a much higher resistance to fPrV challenge after immunization of the mice with aPrV vaccine. This study offers convincing experimental evidence that an injection of Se with oral GSLS is a promising adjuvant combination that improves the efficacy of vaccination against PrV and deserves further study regarding improvement of responses to other animal vaccines.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Herpesvirus Suídeo 1/imunologia , Panax/química , Folhas de Planta/química , Vacinas contra Pseudorraiva/imunologia , Saponinas/farmacologia , Selênio/farmacologia , Vacinas Atenuadas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Formação de Anticorpos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Combinação de Medicamentos , Feminino , Febre Aftosa/prevenção & controle , Imunização , Imunoglobulina G/sangue , Células Matadoras Naturais/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Doença de Newcastle/prevenção & controle , Extratos Vegetais/farmacocinética , Pseudorraiva/prevenção & controle , Saponinas/administração & dosagem , Selênio/administração & dosagem , Vacinação , Vacinas Atenuadas/administração & dosagem
15.
Int J Mol Sci ; 20(10)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100828

RESUMO

In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Lipídeos/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , Medula Óssea , Progressão da Doença , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/imunologia , Ácidos Graxos Ômega-6/uso terapêutico , Ácidos Graxos Insaturados , Neoplasias Hematológicas/tratamento farmacológico , Hematopoese , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoterapia , Inflamação , Leucemia Mieloide Aguda/imunologia , Lipídeos/imunologia , Neoplasias/tratamento farmacológico , Prognóstico , Microambiente Tumoral
16.
Expert Opin Ther Pat ; 29(5): 339-351, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31064237

RESUMO

INTRODUCTION: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system. AREAS COVERED: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms. EXPERT OPINION: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure-activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production.


Assuntos
Compostos de Boro/farmacologia , Fatores Imunológicos/farmacologia , Inflamação/tratamento farmacológico , Imunidade Adaptativa/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Compostos de Boro/química , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/química , Inflamação/imunologia , Patentes como Assunto , Relação Estrutura-Atividade
17.
Nutrients ; 11(4)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022989

RESUMO

The study aimed to investigate the immunomodulatory activity of oligopeptides derivedfrom oat (Avena Nuda L.) (OOPs). Healthy female BALB/c mice were randomly assigned to fivegroups, given deionized water (control) and 0.25, 0.5, 1.0, and 2.0 g/kg body weight (BW) of OOPsdaily by intragastric administration. Seven assays were performed to determine theimmunomodulatory effects of OOPs on immune organ ratios, cellular and humoral immuneresponses, macrophage phagocytosis, and natural killer (NK) cell activity. Spleen T lymphocytesubpopulations (by flow cytometry), serum cytokine and immunoglobulin levels (by multiplexsandwich immunoassays) were determined to evaluate how OOPs affected the immune system.Our results showed that OOPs could significantly improve innate and adaptive immune responsesin mice through the enhancement of cell-mediated and humoral immunity, macrophagephagocytosis capacity, and NK cell activity. We concluded that the immunomodulatory effectsmight be attributed to increased T and Th cell percentages, serum interferon (IFN)-γ, interleukin(IL)-1 α, IL-2, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)- α, and granulocyte-macrophagecolony-stimulating factor (GM-CSF) secretions as well as immunoglobulin (Ig) A, IgG, and IgMproductions. These results indicate that dietary OOPs could be considered as promisingimmunomodulators with dosages ranging from 0.25 to 2.0 g/kg BW.


Assuntos
Anticorpos/metabolismo , Avena/química , Citocinas/metabolismo , Imunidade Inata/efeitos dos fármacos , Oligopeptídeos/farmacologia , Subpopulações de Linfócitos T/fisiologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Anticorpos/genética , Avena/classificação , Proliferação de Células/efeitos dos fármacos , Citocinas/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipersensibilidade Tardia , Macrófagos , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/química , Fagocitose , Baço/citologia
18.
J Anim Sci ; 97(7): 2989-3006, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31011748

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is the most prevalent disease of swine globally. Infection of weanling pigs with PRRSV leads to a complex immune response resulting in significant disease and decreased growth performance. Previous experimental evidence suggests that increasing concentrations of soybean meal in the diet of young pigs confer benefits in terms of growth performance and immune parameters. The objective of this experiment was to identify potential modes of action for this benefit, specifically the ability for soy-derived isoflavones (ISF) to confer immunological benefits to young pigs infected with PRRSV. Four dietary treatments differing in soy protein source (soy protein concentrate vs. enzyme-treated soybean meal) and ISF supplementation (none vs. 1,500 mg total ISF/kg) were fed; the control diet (CON) contained soy protein concentrate and no supplemental ISF. Weanling pigs (60 barrows, 21 d of age, 5.71 ± 0.44 kg) from a naturally Mycoplasma hyopneumoniae (Mh)-infected source herd were individually housed in disease containment chambers and provided ad libitum access to experimental diets for 7 d before receiving either a sham inoculation or a 9.28 × 103 50% tissue culture infective dose of PRRSV at 28 d of age (0 d postinoculation). A total of 5 experimental treatments included an uninfected group receiving the CON diet, plus four infected groups each receiving a different dietary treatment. Growth performance and rectal temperatures were recorded throughout the study, and blood was collected for quantification of serum PRRSV load, presence of anti-PRRSV antibodies, differential complete blood counts, cytokine concentrations, and T-cell immunophenotyping. Data were analyzed as a 2-way or 3-way ANOVA for all treatments including PRRSV-infected pigs, in addition to a single degree of freedom contrast to compare uninfected and infected pigs receiving the CON diet. PRRSV-infection reduced growth rate and efficiency compared with noninfected controls with minimal influences by ISF. Supplemental ISF reduced PRRSV-induced band neutrophilia and improved cytotoxic-to-helper T-cell ratios. These results suggest that ISF contribute to activation of adaptive immune system pathways and could benefit recovery from and clearance of PRRSV infections.


Assuntos
Suplementos Nutricionais/análise , Isoflavonas/farmacologia , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Proteínas de Soja/farmacologia , Soja/química , Imunidade Adaptativa/efeitos dos fármacos , Ração Animal/análise , Animais , Citocinas/sangue , Dieta/veterinária , Masculino , Mycoplasma hyopneumoniae/isolamento & purificação , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Suínos , Carga Viral/veterinária , Desmame
19.
Nat Commun ; 10(1): 1899, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015397

RESUMO

Nanoparticles can potentially stimulate tumour microenvironments to elicit antitumour immunity. Herein, we demonstrate effective immunotherapy of colorectal cancer via systemic delivery of an immunostimulatory chemotherapeutic combination in nanoscale coordination polymer (NCP) core-shell particles. Oxaliplatin and dihydroartemesinin have contrasting physicochemical properties but strong synergy in reactive oxygen species (ROS) generation and anticancer activity. The combined ROS generation is harnessed for immune activation to synergize with an anti-PD-L1 antibody for the treatment of murine colorectal cancer tumours. The favourable biodistribution and tumour uptake of NCPs and the absence of peripheral neuropathy allow for repeated dosing to afford 100% tumour eradication. The involvement of innate and adaptive immune systems elicit strong and long lasting antitumour immunity which prevents tumour formation when cured mice are challenged with cancer cells. The intrinsically biodegradable, well tolerated, and systemically available immunostimulatory NCP promises to enter clinical testing as an immunotherapy against colorectal cancer.


Assuntos
Adenocarcinoma/terapia , Vacinas Anticâncer/farmacologia , Neoplasias Colorretais/terapia , Fatores Imunológicos/farmacologia , Nanopartículas/administração & dosagem , Polímeros/administração & dosagem , Imunidade Adaptativa/efeitos dos fármacos , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Animais , Anticorpos Neutralizantes/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Artemisininas/farmacocinética , Artemisininas/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Vacinas Anticâncer/síntese química , Vacinas Anticâncer/farmacocinética , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Composição de Medicamentos/métodos , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/síntese química , Fatores Imunológicos/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Transplante de Neoplasias , Oxaliplatina/farmacocinética , Oxaliplatina/farmacologia , Polímeros/síntese química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Análise de Sobrevida , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
20.
Arch Immunol Ther Exp (Warsz) ; 67(3): 133-141, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30976817

RESUMO

Pattern recognition receptors (PRRs) are members of innate immunity, playing pivotal role in several immunological reactions. They are known to act as a bridge between innate and adaptive immunity. They are expressed on several normal cell types but have been shown with increasing frequency on/in tumor cells. Significance of this phenomenon is largely unknown, but it has been shown by several authors that they, predominantly Toll-like receptors (TLRs), act in the interest of tumor, by promotion of its growth and spreading. Preparation of artificial of TLRs ligands (agonists) paved the way to use them as a therapeutic agents for cancer, so far in a limited scale. Agonists may be combined with conventional anti-cancer modalities with apparently promising results. PRRs recognizing nucleic acids such as RIG-1 like receptors (sensing RNA) and STING (sensing DNA) constitute a novel promising approach for cancer immunotherapy.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Imunoterapia/métodos , Neoplasias/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Imunidade Adaptativa/efeitos dos fármacos , Animais , Antineoplásicos Imunológicos/uso terapêutico , DNA/imunologia , DNA/metabolismo , Modelos Animais de Doenças , Humanos , Imunidade Inata/efeitos dos fármacos , Ligantes , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , RNA/imunologia , RNA/metabolismo , Receptores de Reconhecimento de Padrão/agonistas , Receptores de Reconhecimento de Padrão/imunologia
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