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1.
Life Sci ; 241: 117168, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31838133

RESUMO

AIM: Immunosenescence is the decline of the host immune system due to aging, resulting in various complications. The splenic lymphoid nodule is the pivotal compartment involved in immunosenescence. In this study, we investigated the important changes in the splenic immune cell populations of aged rats (18-24 months) in comparison with young rats (3-5 months). MATERIALS AND METHODS: We, also, studied the effects of aging on the activities of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels in spleen of both groups, besides the changes of the splenic architecture. Furthermore, immunohistochemical staining was performed to detect the aging effects in T cells, B cells, macrophages, granulocytes, mast cells, proliferating cells, apoptotic cells, and cells positive for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and Toll-like receptor 4 (TLR4). KEY FINDINGS: The aged rats had significantly lower spleen/body weight ratios and smaller splenic nodules, indicating a decline in general immunity in them. With aging, T-SOD activities were decreased, while MDA levels were increased, exhibiting that oxidative stress increases in spleens. In addition, the aged group also had significantly fewer T and B cells, macrophages, granulocytes, IL-6 and TLR4 immuno-positive cells, and proliferating cells in the periarterial lymphatic sheaths, marginal zone, and lymphoid follicles compared with the young group. On the other hand, the number of mast cells and apoptotic cells was significantly increased with age. Therefore, we can conclude that cellular immunity and humoral immunity were crumpled with age.


Assuntos
Linfócitos B/imunologia , Imunidade Celular/imunologia , Imunossenescência/imunologia , Estresse Oxidativo/imunologia , Baço/imunologia , Linfócitos T/imunologia , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Células Cultivadas , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Baço/metabolismo , Baço/patologia , Superóxido Dismutase/metabolismo , Linfócitos T/metabolismo , Linfócitos T/patologia
2.
Nat Commun ; 10(1): 4097, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506438

RESUMO

Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics. However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive. To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets. We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL). By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes. To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice. Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation. Collectively, our study underlines the importance of including environmental factors in genetic association studies.


Assuntos
Cruzamentos Genéticos , Dieta , Genes , Estudos de Associação Genética , Característica Quantitativa Herdável , Animais , Animais não Endogâmicos , Anticorpos Antinucleares/genética , Bactérias/crescimento & desenvolvimento , Biodiversidade , Feminino , Fungos/crescimento & desenvolvimento , Predisposição Genética para Doença , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Masculino , Camundongos , Microbiota , Mapeamento Físico do Cromossomo , Locos de Características Quantitativas/genética , Baço/metabolismo , Transcriptoma/genética , Sequenciamento Completo do Genoma
3.
An Acad Bras Cienc ; 91(3): e20181330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508665

RESUMO

Type 1 diabetes (T1D) is the result of the selective destruction of the pancreatic ß-cells by T cells of the immune system. Although spleen is a secondary lymphoid organ, it is also involved in the T1D pathogenesis. However, the alterations in a variety of cellular processes of this disease need to be further understood. We aimed to analyze the benefits of resveratrol, and its complexed form on diabetic complications in the spleen of rats. To this end, we investigated important enzymes of phosphoryl transfer network, and Na+, K+-ATPase activity. Wistar rats were divided into non-diabetic groups: Control, Ethanol, Resveratrol, Hydroxypropyl-ß-cyclodextrin, Resveratrol-hydroxypropyl-ß-cyclodextrin, and diabetic groups with the same treatments. Diabetes was induced by a single dose of 60 mg/kg of streptozocin intraperitoneally, and treatments by intragastric gavage once daily for 60 days. Hyperglycemia reduced creatine kinase activity, which was reversed by the administration of resveratrol. Na+, K+-ATPase activity was greatly affected, but it was reversed by resveratrol and resveratrol-hydroxypropyl-ß-cyclodextrin. This suggest an energetic imbalance in the spleen of diabetic rats, and in case this also occurs in the diabetic patients, it is possible that resveratrol supplementation could be beneficial to the better functioning of the spleen in diabetic patients.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Resveratrol/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Baço/metabolismo , Animais , Antioxidantes/metabolismo , Glicemia/análise , Peso Corporal , Creatina Quinase/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Metabolismo Energético/efeitos dos fármacos , Hiperglicemia/metabolismo , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Estreptozocina
4.
Int J Med Sci ; 16(8): 1116-1122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523174

RESUMO

This study investigated the anti-allergic effect of Poncirus trifoliata (L.) Raf. (PT) on human keratinocytic HaCaT cells in vitro and on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like lesions in vivo. The release of TARC, MCP-1, IL-6 and IL-8 is increased by IFN-γ and TNF-α in HaCaT cells, and PT extract suppressed the increased production of TARC, MCP-1, IL-6, and IL-8. PT extract recovered the expression of filaggrin decreased by IFN-γ and TNF-α. in vivo experiment, PT administration decreased the skin severity score, thickening of the epidermis, movement of inflammatory cells into the dermis, and serum IgE level as compared to DNCB treatment. Moreover, the decrease of filaggrin and loricrin induced by DNCB treatment was recovered by PT administration. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased after treatment with concanavalin A, and the secretions of IL-4, IL-5, IL-13 and eotaxin were lower in the PT-treated group than in the DNCB group. These findings may indicate that PT is useful in drug development for the treatment of AD.


Assuntos
Dermatite Atópica/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Extratos Vegetais/farmacologia , Poncirus/química , Animais , Linhagem Celular , Quimiocina CCL11/metabolismo , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Dinitroclorobenzeno/toxicidade , Feminino , Humanos , Imunoglobulina E/sangue , Interferon gama/farmacologia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos , Proteínas S100/metabolismo , Baço/citologia , Baço/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
5.
APMIS ; 127(12): 797-804, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31514254

RESUMO

Brucellosis is a worldwide bacterial zoonosis caused by Brucella spp. No approved vaccine is available for human use against the disease. In this study, outer membrane vesicles (OMVs) from a Brucella melitensis biovar 1 human isolate obtained in Iran were used to immunize BALB/c mice (n = 12) by 2 intramuscular injections with a 2-week interval. Another group of 12 mice was used as non-vaccinated controls. Two weeks after the last vaccination, six mice of each group were sacrificed, and proliferation and interferon gamma (IFNγ) production responses of their splenocytes were evaluated following in vitro stimulation with killed Brucella cells. The other mice were challenged with the virulent B. melitensis isolate. Two weeks later, mice were killed and spleens were cultured to determine the number of the challenge strain. The results showed proliferative response and IFNγ production of splenocytes from vaccinated mice (stimulation index: 2.18 ± 0.57, and 1519.35 ± 10.70 pg/mL, respectively) were significantly higher than those of control mice (stimulation index: 1.02 ± 0.02, and 210.01 ± 17.58 pg/mL, respectively). Numbers of the challenge strain in spleens of vaccinated mice were also significantly less than those in the controls with 1.6 units of protection. Our study revealed vaccination with OMVs of the B. melitensis isolate could induce specific immune responses and protection against infection in the mouse model suggesting their potential application for active immunization against brucellosis.


Assuntos
Vacina contra Brucelose/imunologia , Brucella melitensis/imunologia , Brucelose/imunologia , Brucelose/prevenção & controle , Vesículas Extracelulares/imunologia , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Brucella melitensis/citologia , Brucelose/microbiologia , Modelos Animais de Doenças , Feminino , Humanos , Imunidade Celular , Interferon gama/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Baço/metabolismo , Baço/microbiologia , Vacinação
6.
Anal Chim Acta ; 1082: 18-29, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472707

RESUMO

Information on the risk of exposure to cerium oxide (CeO2) nanoparticles (NPs) is limited. To assess risk, we must know where and how such NPs are distributed to the body after exposure, both short- and long-term. In this work, an integrated approach of quantitative LA-ICP-MS bioimaging and fractionation was employed to study the translocation and transformation of CeO2 and Ce3+ in mouse spleen and liver. The complementary information retrieved by the two techniques above on the accumulation of Ce and dissolution/aggregation were found consistent. In brief, a detailed fine scanning of a region of interest in the organ was performed after fast-screening at low spatial resolution. In the spleen, after short-term high-dose exposure, CeO2 NPs was found mainly in the marginal zone and caused an up-regulation of Zn in the white pulp. After long-term low-dose exposure, CeO2 was found in the marginal zone and white pulp. In the liver, CeO2 NPs were mainly distributed in the Kupffer cells and lobule periphery. The high spatial resolution LA maps of H&E-stained liver sections allowed imaging close to cell level; this enabled an estimation of Ce content in Kupffer cells. Furthermore, fractionation by ultrafiltration was also employed to differentiate the ionic and NP species in the organs. This fractionation showed aggregation of Ce ions in spleen, supporting the LA-ICP-MS results. Transmission electron microscopy revealed that long-term CeO2 exposure triggered an immune response to infection in the spleen and confirmed the differential deposition of Ce in the marginal zone. The integrated analyses based on ICP-MS together with histology and TEM investigation suggests that long-term low doses of CeO2 NPs may cause toxicity in the liver and impair functions of the immune system.


Assuntos
Cério/análise , Cério/farmacocinética , Fígado/metabolismo , Nanopartículas Metálicas/química , Baço/metabolismo , Animais , Cério/toxicidade , Fracionamento Químico/métodos , Cobre/metabolismo , Limite de Detecção , Fígado/patologia , Masculino , Espectrometria de Massas/métodos , Nanopartículas Metálicas/toxicidade , Camundongos Endogâmicos ICR , Baço/patologia , Zinco/metabolismo
7.
BMC Genomics ; 20(1): 647, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412766

RESUMO

BACKGROUND: Despite the convergence of rapid technological advances in genomics and the maturing field of ecoimmunology, our understanding of the genes that regulate immunity in wild populations is still nascent. Previous work to assess immune function has relied upon relatively crude measures of immunocompetence. However, with next-generation RNA-sequencing, it is now possible to create a profile of gene expression in response to an immune challenge. In this study, captive zebra finch (Taeniopygia guttata; adult males) were challenged with bacterial lipopolysaccharide (LPS) or vehicle to stimulate the innate immune system. 2 hours after injection, birds were euthanized and hypothalami, spleen, and red blood cells (RBCs) were collected. Taking advantage of the fully sequenced genome of zebra finch, total RNA was isolated, sequenced, and partially annotated in these tissue/cells. RESULTS: In hypothalamus, there were 707 significantly upregulated transcripts, as well as 564 and 144 in the spleen and RBCs, respectively, relative to controls. Also, 155 transcripts in the hypothalamus, 606 in the spleen, and 61 in the RBCs were significantly downregulated. More specifically, a number of immunity-related transcripts (e.g., IL-1ß, RSAD2, SOCS3) were upregulated among tissues/cells. Additionally, transcripts involved in metabolic processes (APOD, LRAT, RBP4) were downregulated. CONCLUSIONS: These results suggest a potential trade-off in expression of genes that regulate immunity and metabolism in birds challenged with LPS. This finding is consistent with a hypothermic response to LPS treatment in small birds. Unlike mammals, birds have nucleated RBCs, and these results support a novel transcriptomic response of avian RBCs to immune challenge.


Assuntos
Tentilhões/genética , Tentilhões/imunologia , Perfilação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Animais , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Eritrócitos/metabolismo , Ontologia Genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/imunologia , Hipotálamo/metabolismo , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia
8.
Int J Nanomedicine ; 14: 5175-5186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409986

RESUMO

Background: As a promising nanomaterial for biomedical applications, zirconia nanoparticles (ZrO2) have aroused concern recently, but the toxicity of ZrO2 in vivo has received little attention. Purpose: The aim of this study is to demonstrate the systematic single dose toxicity, biodistribution and oxidative damage of ZrO2 in vivo after intravenous injection in mice. Materials and methods: Ten ICR mice were used at the high dose of ZrO2 including 600, 500, 400 and 300mg/kg. Maximum tolerated dose (MTD) of 150 nm ZrO2 was determined as 500mg/kg. Hematology analysis and blood biochemical assay were determined for the evaluation of oxidative damage caused by ZrO2. Biodistribution of ZrO2 was investigated by ICP-OES and TEM. Results: Mice treated with higher dose (500mg/kg) showed significant spread in white blood cell counts (p<0.05). Especially, the serum ALT levels of 500mg/kg groups increased significantly (p<0.05) compared with the control group. ZrO2 particles would not induce any changes in appearance and micromorphology of liver at 100 and 350mg/kg. Spleen samples showed no significant changes in micromorphology of the lymphoid follicles and in the size of the red pulp after injection of ZrO2 at all doses. The serum of ZrO2-treated animals (350 and 500mg/kg) has reduced levels of SOD compared to the control group (p<0.05). ZrO2 persists in membrane-enclosed vesicles called lysosomes in the liver and spleen macrophages without abnormal changes of ultrastructure. Conclusion: These findings would contribute to the future development of ZrO2-based drug delivery system and other biomedical applications.


Assuntos
Nanopartículas/administração & dosagem , Nanopartículas/toxicidade , Estresse Oxidativo , Zircônio/administração & dosagem , Zircônio/toxicidade , Animais , Sistemas de Liberação de Medicamentos , Feminino , Injeções Intravenosas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos ICR , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Baço/metabolismo , Distribuição Tecidual/efeitos dos fármacos
9.
J Med Food ; 22(9): 937-943, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31448992

RESUMO

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) has been reported to have beneficial effects on regulation of immune responses in mammals and poultry. Nonetheless, the immunoregulatory mechanism of action of PAMK remains unclear. The Toll-like receptor 4 (TLR4) signaling cascade has been proved as a classic polysaccharide-regulated pathway. The aim of this study was to explore the effects of PAMK on the TLR4 signaling pathway in the regulation of spleen function in mice. Ninety-six 5-week-old BALB/c female mice were randomly allocated into four groups with three replicates per group and eight mice per replicate in a single-factor completely randomized experimental design. The control group was fed a basic diet (PAMK free); the other three groups were fed 100, 200, or 400 mg/kg PAMK for 28 days. The spleen index, concentrations of cytokines, and mRNA and protein expression levels of genes related to TLR4 signaling were determined in spleen tissue. Compared with the control group, the spleen index significantly increased in all treatment groups. Concentrations of interleukin 2 (IL-2), IL-4, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) in the medium-PAMK group also increased significantly. PAMK in the medium-PAMK group significantly increased both mRNA and protein expression of TLR4, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 (TRAF6), TRAF3, and nuclear factor kappa B (NF-κB) in the spleen. In conclusion, PAMK may increase immune-response capacity of the spleen in mice via TLR4-MyD88-NF-κB signaling.


Assuntos
Atractylodes/química , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Polissacarídeos/administração & dosagem , Baço/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Feminino , Interleucina-2/genética , Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Baço/metabolismo , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Fish Shellfish Immunol ; 93: 888-894, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31425830

RESUMO

Sturgeons represent a substantial scientific interest due to their high economic value, endangered status and also as the most primitive group of ray-finned fishes. Rapid progress in knowledge of sturgeon immunity was achieved recently with use of RNA sequencing. We report transcriptome sequencing of gill, head kidney, and spleen of bester sturgeon (a hybrid of beluga Huso huso and sterlet Acipenser ruthenus) injected with synthetic double-stranded RNA (polyI:C). The composition of transcriptome and responses to treatment were examined in the context of comparative genomics with focus on immune genes. Sturgeon transcripts matched to 21.5 k different proteins (blastx). With reference to Atlantic salmon, the functional groups and pathways of the immune system were uniformly represented: at average 36.5 ±â€¯0.8% genes were found. Immune genes comprise a significant fraction of transcriptome. Among twenty genes with highest transcription levels, five are specialized immune genes and two encode heme and iron binding proteins (serotransferrin and hemopexin) also known as acute phase proteins. Challenge induced multiple functional groups including apoptosis, cell cycle and a number of metabolic pathways. Treatment stimulated innate antiviral immunity, which is well conserved between sturgeon and salmon, the most responsive genes were mx, rsad2 (viperin), interferon induced protein 44 and protein with tetratricopeptide repeats 5, cd87 and receptor transporting protein 3. Results added to knowledge of immune phylogeny. Gain and loss of genes was assessed by comparison with genomes from different phylogenetic groups. Among differentially expressed genes, percentage of acquired and lost genes was much lower in comparison with genes present in all vertebrates. Innate antiviral immunity was subject to the greatest changes in evolution of jawed vertebrates. A significant fraction of genes (15%) was lost in mammals and only half of genes is annotated in public databases as involved in antiviral responses. Change of function may have an important role in evolution of immunity together with gain and loss of genes.


Assuntos
Peixes/genética , Peixes/imunologia , Imunidade Inata/genética , Transcriptoma/imunologia , Animais , Perfilação da Expressão Gênica/veterinária , Brânquias/metabolismo , Rim Cefálico/metabolismo , Imunogenética , Poli I-C/farmacologia , Análise de Sequência de RNA/veterinária , Baço/metabolismo
11.
Exp Parasitol ; 205: 107736, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442455

RESUMO

Goats are frequently described as an intermediate host for the protozoan Neospora caninum, manifesting the disease mainly by recurrent abortions with placentitis and encephalitis in fetuses. Several reports of natural and experimental infections in cattle and mice show differences in the immune response, and the outcome of the infection can be variable depending on the species affected and by the behavior of the infective strain. This study describes for the first time two Neospora caninum strains isolated from naturally infected goats from the state of Minas Gerais, Brazil. One placenta and one brain from different goats were processed for a first bioassay in gerbils (Meriones unguiculatus). Subsequently, a second bioassay was performed by inoculating the processed brain samples from gerbils into Interferon gamma (IFN-γ) knockout mice (KO mice). Tachyzoites collected from the peritoneal fluid of the KO mice were inoculated into VERO cell monolayers, where they presented a very slow growth rate. The tachyzoites were also inoculated into BALB/c mice with a dose of 106 tachyzoites per animal. After a 5-week follow up, the animals infected with both of the strains developed a strong polarized Th1 response with increased serum and spleen gene expression levels of pro-inflammatory cytokines (mainly IFN-γ and TNF-α) in the first week. Tissue lesions were mild in the animals infected with both strains. Despite the strong immune response preventing an infection in the visceral organs, the parasite was able to reach the brain, causing progressive brain lesions from the second to fifth week post infection. The NC-goat1-infected mice presented with severe meningoencephalitis, but the NC-goat2-infected animals had considerable histological brain lesions only at week 5. Immunohistochemical analysis of the mouse brains revealed a different pattern of inflammatory cells compared to the naturally infected goats. A severe inflammatory infiltrate of CD3+ T lymphocytes was found in the NC-goat1-infected mice. A more discrete infiltrate of CD3+ T cells was found in the NC-goat2-infected animals. Additionally, IBA1 IHC revealed an intense microglial reaction and monocyte perivascular cuffs in the NC-goat1-infected animals and lower microglia/monocyte infiltrates in the NC-goat2-infected mice. This work contributes knowledge on the pathogenicity of new Neospora caninum strains in mice, comparable with other well-established mouse models of the disease, and demonstrates the importance of studying goats as an intermediate host of this parasite.


Assuntos
Coccidiose/veterinária , Doenças das Cabras/parasitologia , Neospora/patogenicidade , Animais , Bioensaio/veterinária , Encéfalo/parasitologia , Encéfalo/patologia , Coccidiose/parasitologia , Coccidiose/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Gerbillinae , Doenças das Cabras/patologia , Cabras , Imuno-Histoquímica/veterinária , Interferon gama/genética , Interferon gama/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neospora/isolamento & purificação , Pâncreas/patologia , Placenta/patologia , Gravidez , Baço/metabolismo , Baço/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Células Vero
12.
Fish Shellfish Immunol ; 93: 694-701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421240

RESUMO

The present study investigated the effects of dietary anthocyanin on the growth performance, haematological, non-specific immune, and spleen gene expression responses of Nile tilapia, Oreochromis niloticus. Five experimental groups of fish with mean weights of 8.24 ±â€¯0.64 g were used in the study; four of these were fed with diets incorporating anthocyanin (20 mg kg -1, 40 mg kg-1, 80 mg kg-1 and 160 mg kg-1), while the fifth was a control group without dietary anthocyanin. Growth performance and haematological parameters of tilapia were not affected by anthocyanin-supplemented diets (p > 0.05). Dietary anthocyanin significantly increased respiratory burst activity, phagocytic activity, phagocytic index, lysozyme activity, myeloperoxidase activity, serum total superoxide dismutase (T.SOD) activity, and serum catalase (CAT) activity (p < 0.05). The total immunoglobulin level was highest in the 80 mg kg-1 group compared with the other groups (p < 0.05). In addition, with the anthocyanin-containing diets, the gene levels of interleukin 1, beta (IL-1ß), interleukin 8 (IL-8), tumor necrosis factor (TNF-α), heat shock protein 70 (HSP70), and interferon gamma (IFN-γ) were increased in the fish spleen, and the gene levels of CAT, GPx, and SOD were also increased in fish liver (p < 0.05). At the end of the experiment, the fish were subjected to ammonia stress. The groups fed with 20 and 40 mg kg-1 anthocyanin exhibited higher survival rates than the other groups. In summary, feeding Nile tilapia with anthocyanin-containing diets caused increases in the innate immune parameters, gene expression responses, and the survival rate of the fish subjected to ammonia stress.


Assuntos
Amônia/metabolismo , Antocianinas/metabolismo , Ciclídeos/imunologia , Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Ração Animal/análise , Animais , Antocianinas/administração & dosagem , Ciclídeos/sangue , Ciclídeos/genética , Ciclídeos/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Poluentes Químicos da Água
13.
Microb Pathog ; 135: 103649, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374321

RESUMO

Extracellular adenosine triphosphate (ATP) is as key mediator of immune and inflammatory responses. ATP is normally sequestered in the intracellular milieu and released by apoptotic and necrotic cells, where it acts as a pro-inflammatory mediator in the extracellular milieu. A limited number of studies have explored the involvement of purinergic signaling in oomycete infections, including Saprolegnia parasitica; this is a most destructive oomycete pathogen, associated with high mortality and severe economic losses for fish producers. The aim of this study was to determine whether purinergic signaling exerts anti- or pro-inflammatory effects in spleens of grass carp (Ctenopharyngodon idella) naturally infected by S. parasitica. Animals naturally infected with S. parasitica showed typical gross lesions characterized by cotton-wool tufts on the tail and fins, as well as severe histopathological lesions such as necrosis. Spleen ATP and metabolites of nitric oxide (NOx) levels were higher in fish naturally infected by S. parasitica compared to control on day 7 post-infection (PI). Spleen nucleoside triphosphate diphosphohydrolase (NTPDase) activity (ATP as substrate) was greater in fish naturally infected by S. parasitica than in uninfected on day 7 PI, while no significant differences were observed between groups with respect to NTPDase (adenosine diphosphate as substrate) and 5'-nucleotidase activities. Finally, adenosine deaminase (ADA) activity was lower in fish naturally infected by S. parasitica than in uninfected fish on day 7 PI. In summary, spleen tissue necrosis in the context of saprolegniosis provokes an intense release of ATP into the extracellular milieu, where it interacts with the P2X7 purine receptor and leads to a self-sustained pro-inflammatory deleterious cycle, contributing to an intense inflammatory process. In response to excessive ATP levels in the extracellular milieu, ATP and adenosine hydrolysis were modulated in an attempt to restrict the inflammatory process via upregulation of NTPDase and downregulation of ADA activities. We conclude that the purinergic signaling pathway modulates immune and inflammatory responses during natural infection with S. parasitica.


Assuntos
Trifosfato de Adenosina/metabolismo , Anti-Inflamatórios/metabolismo , Carpas/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/parasitologia , Purinérgicos/metabolismo , Transdução de Sinais , Baço/metabolismo , Adenosina Desaminase/metabolismo , Animais , Carpas/metabolismo , Modelos Animais de Doenças , Doenças dos Peixes/patologia , Proteínas de Peixes/imunologia , Micoses , Necrose , Óxido Nítrico/metabolismo , Saprolegnia/patogenicidade , Baço/patologia
14.
Mar Drugs ; 17(8)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362412

RESUMO

Immunomodulation involves two mechanisms, immunostimulation and immunosuppression. It is a complex mechanism that regulates the pathophysiology and pathogenesis of various diseases affecting the immune system. Immunomodulators can be used as immunostimulators to reduce the side effects of drugs that induce immunosuppression. In this study, we characterized the chemical composition of high molecular weight fucoidan (HMWF) and low molecular weight fucoidan and compared their functions as natural killer (NK) cell-derived immunostimulators in vitro. We also tested the effectiveness of HMWF, which has a relatively high function in vitro, as an immunostimulator in immunosuppressed animal models. In these models, HWMF significantly restored NK cell cytotoxicity and granzyme B release to the control group level. In addition, the expression of interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α also increased in the spleen. This study suggests that HMWF acts as an effective immunostimulant under immunosuppressive conditions.


Assuntos
Ciclofosfamida/farmacologia , Tolerância Imunológica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Polissacarídeos/farmacologia , Undaria/química , Animais , Linhagem Celular , Citocinas/metabolismo , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Baço/efeitos dos fármacos , Baço/metabolismo
15.
Food Chem Toxicol ; 133: 110748, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377140

RESUMO

Hexavalent chromium raises high concern because of its wide industrial applications and reported toxicity. Long-term (135 days) oral exposure of Wistar rats to chromium in the form of K2Cr2O7 (exposed group~20 mg/kg/day) led to a decrease in thymus mass and thymocytes' number and caused structural and functional changes in the lymph nodes and spleen, namely lymphoreticular hyperplasia and plasmocytic macrophage transformation. Programmed cell death was increased in both thymocytes and splenocytes and decreased in lymphocytes in the T-zones of spleen and lymph nodes. Moreover, Cr (VI) administration decreased myeloid cells' and neutrophils' number, while it increased lymphoid and erythroid cells' number in bone marrow. Cr (VI) immune system effects seem to be related to oxidative stress induction, as depicted by the increased levels of diene conjugates and malondialdehyde in the spleen and liver and by the decreased activity of catalase and superoxide dismutase in rats' erythrocytes. In addition, exposure to Cr (VI) decreased copper, nickel and iron concentrations in blood and liver, while Cr levels in blood, spleen and liver were increased, as expected. The observed changes in the series of immunological parameters studied contribute to the development of new approaches for the prevention of low level Cr exposure toxicity.


Assuntos
Cromo/toxicidade , Linfonodos/efeitos dos fármacos , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Imuno-Histoquímica , Linfonodos/metabolismo , Contagem de Linfócitos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Baço/metabolismo , Linfócitos T/metabolismo , Timócitos/metabolismo , Timo/metabolismo , Timo/patologia
16.
Int J Mol Sci ; 20(15)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387229

RESUMO

Inflammatory bowel disease (IBD) is a worldwide healthcare problem calling for the development of new therapeutic drugs. Angelica sinensis and Zingiber officinale Roscoe are two common dietetic Chinese herbs, which are traditionally used for complementary treatment of gastrointestinal disorders. As bioactive constituents, volatile and pungent substances of these two herbs could be effectively extracted together by supercritical fluid extraction. In this study, the supercritical fluid extract of Angelica sinensis and Zingiber officinale Roscoe (AZ-SFE) was obtained by an optimized extraction process and it was chemically characterized. The anti-inflammatory effect and underlying mechanism of AZ-SFE were evaluated in a lipopolysaccharide (LPS)-induced RAW264.7 cell model and a 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model. AZ-SFE notably inhibited the production of NO in LPS-stimulated macrophages, and it inhibited the proliferation of Concanavalin A (Con A)-induced splenocytes with suppression of the Th1 immune response. In vivo, the study demonstrated that AZ-SFE significantly alleviated disease activity, colonic shortening, macroscopic damage and histological injury of TNBS-treated rats with reduction of oxidative stress, suppression of inflammatory cytokines, and modulation of hepcidin and serum iron. These findings suggested that AZ-SFE may be a promising supplement for current IBD therapy.


Assuntos
Angelica sinensis/química , Anti-Inflamatórios não Esteroides/farmacologia , Colite/tratamento farmacológico , Gengibre/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Biomarcadores , Biópsia , Sobrevivência Celular/efeitos dos fármacos , Cromatografia com Fluido Supercrítico , Colite/etiologia , Colite/metabolismo , Citocinas/biossíntese , Modelos Animais de Doenças , Cromatografia Gasosa-Espectrometria de Massas , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Ratos , Baço/imunologia , Baço/metabolismo , Ácido Trinitrobenzenossulfônico/efeitos adversos
17.
Fish Shellfish Immunol ; 93: 344-353, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352116

RESUMO

Large yellow croaker (Larimichthys crocea) is an economical important farmed fish in China. "Visceral White Spot Disease" caused by Pseudomonas plecoglossicida is a disease with a high mortality rate in cage-cultured L. crocea in recent years and resulted in heavy economy lossess. The dual RNA-seq results of previous study showed that the expression of clpV gene in P. plecoglossicida was significantly up-regulated during infection. RNAi significantly reduced the expression of clpV in P. plecoglossicida with maximum silencing efficiency of 96.1%. Compared with the wild type strain, infection of clpV-RNAi strain resulted in a delayed onset time and a 25% reduction in mortality of L. crocea, as well as lessening the symptoms of the spleen. The results of dual RNA-seq of L. crocea infected by clpV-RNAi strain of P. plecoglossicida changed considerably, compared with the counterpart infected with the wild strain. The KEGG enrichment analysis showed that Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, C-type lectin receptor signaling pathway and MAPK signaling pathway of L. crocea were most affected by the silence of clpV in P. plecoglossicida. RNAi of clpV resulted in the downregulation of genes in flagella assembly pathway and a weaker immune response of host.


Assuntos
Proteínas de Bactérias/genética , Doenças dos Peixes/imunologia , Interações Hospedeiro-Patógeno/imunologia , Perciformes/imunologia , Transcriptoma/imunologia , Animais , Proteínas de Bactérias/metabolismo , Pseudomonas/fisiologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/veterinária , Interferência de RNA , Baço/metabolismo , Baço/microbiologia
18.
Microb Pathog ; 135: 103622, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323322

RESUMO

Myeloperoxidase (MPO) is a ferrous lysosomal protein with many immune functions that belongs to the heme peroxidase enzyme. In this study, the functions of MPO in the northern snakehead (Channa argus) were investigated by cloning an MPO cDNA sequence with a full length of 3181 bp. Homology analysis showed that northern snakehead MPO gene had the highest (81%) homology with mandarin fish (Siniperca chuatsi). In healthy northern snakehead, the MPO gene was expressed in the head-kidney, kidney, heart, gill, spleen, liver, and muscles but not midgut. After the northern snakehead was infected with Aeromonas veronii, the MPO gene expression varied in different tissues with low level in spleen, liver, gill and muscle, fluctuated in kidney and head-kidney and showed high level in heart. The result indicated that MPO might play an important role in the antimicrobial immune response of the northern snakehead.


Assuntos
Aeromonas veronii/patogenicidade , Doenças dos Peixes/microbiologia , Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/veterinária , Peroxidase/fisiologia , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar , Peixes/genética , Expressão Gênica , Coração , Rim/patologia , Fígado/metabolismo , Músculos/metabolismo , Peroxidase/classificação , Peroxidase/genética , Filogenia , Baço/metabolismo
19.
Mol Immunol ; 114: 72-80, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31344551

RESUMO

Scleroderma is an inflammatory autoimmune disease characterized by extensive tissue fibrosis. The imbalance of effector T (Teff) and regulatory T (Treg) cells and the production of autoantibodies contribute to the pathogenesis of this disease. Metformin (MET) has anti-inflammatory and anti-fibrotic effects, but its effect on the in vivo pathogenesis of scleroderma remains unknown. Therefore, we investigated the potential therapeutic effects of MET treatment of mice with bleomycin (BLM)-induced scleroderma. Scleroderma was induced in female C57BL mice by daily subcutaneous injections of BLM for 28 days. After each 2 h BLM injection, mice received MET (200, 100 or 50 mg/kg) or saline (control) by intraperitoneal injection. At the end of the fourth week, spleen mononuclear cells were collected for flow cytometry analysis. Skin samples were harvested for immunohistochemistry and quantification of other biological parameters.Our results showed that BLM increased dermal thickness, collagen deposition, and hydroxyproline level, and MET markedly mitigated these effects. MET also restored the Treg/Teff cell balance. Accordingly, the level of IL-17A and RORγt (related to Th17 cells) decreased, but Foxp3 (related to Treg function) increased in a dose-dependent manner. In addition, MET treatment inhibited spleen germinal center formation. These results indicate that the immunomodulatory and anti-fibrosis effects of MET on BLM-induced scleroderma are mediated by the upregulation of Treg cell differentiation, inhibition of Teff cell differentiation, and suppression of spleen germinal center formation. These results suggest that MET may be a potential therapeutic for scleroderma.


Assuntos
Bleomicina/farmacologia , Centro Germinativo/efeitos dos fármacos , Metformina/farmacologia , Dermatopatias/induzido quimicamente , Dermatopatias/tratamento farmacológico , Baço/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Centro Germinativo/metabolismo , Hidroxiprolina/metabolismo , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Dermatopatias/metabolismo , Baço/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismo
20.
Fish Physiol Biochem ; 45(4): 1431-1443, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31267430

RESUMO

Connective tissue growth factor (ctgf) is involved in the proliferation, migration, adhesion of cell, and the constituent of extracellular matrix, which plays an important role in embryogenesis, angiogenesis, wound repair, and fibrosis diseases. In this study, the cDNA sequence of grass carp ctgf gene was cloned by rapid amplification of cDNA ends (RACE) method; then, the characteristics of this gene and the predicted protein sequence were analyzed by bioinformatics methods, and the tissue differential expression pattern was detected by the quantitative real-time PCR. The results showed that the grass carp ctgf gene has a full-length of 2223 bp, encoding 343 amino acids. The deduced CTGF protein is a hydrophilic and secretary protein with a molecular mass of 37,978.2 Da and an isoelectric point of 8.22. The signal peptide locates between residue positions 1 and 22 of the polypeptide chain. The protein contains α-helix, ß-strand, and loops. The CTGF protein of grass carp shows a homology of 98%, 96%, 91%, and 91% with Wuchang bream (Megalobrama amblycephala), zebrafish (Danio rerio), common carp (Cyprinus carpio), and Mexican tetra (Astyanax mexicanus). The grass carp ctgf gene expressed significantly higher in blood and spleen than that in other tissues (P < 0.05). The low expression tissues included the heart, gill, skin, muscle, kidney, brain, and intestinal, and the lowest expression tissue was the liver. The results are consistent with the function of this gene.


Assuntos
Carpas/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Proteínas de Peixes/genética , Animais , Clonagem Molecular , Fator de Crescimento do Tecido Conjuntivo/sangue , DNA Complementar/genética , Proteínas de Peixes/sangue , Expressão Gênica , Baço/metabolismo
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