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1.
Mech Ageing Dev ; 207: 111713, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35931241

RESUMO

Inflammaging is a low-grade inflammatory state generated by the aging process that can contribute to frailty and age-related diseases in the elderly. However, it can have distinct effects in the elderly living in endemic areas for infectious diseases. An increased inflammatory response may confer protection against infectious agents in these areas, although this advantage can cause accelerating epigenetic aging. In this study, we evaluated the inflammatory profile and the epigenetic age of infected and noninfected individuals from an endemic area in Brazil. The profile of cytokines, chemokines and growth factors analyzed in the sera of the two groups of individuals showed similarities, although infected individuals had a higher concentration of these mediators. A significant increase in IL-1ra, CXCL8, CCL2, CCL3 and CCL4 production was associated with leprosy infection. Notably, elderly individuals displayed distinct immune responses associated with their infection status when compared to adults suggesting an adaptive remodelling of their immune responses. Epigenetic analysis also showed that there was no difference in epigenetic age between the two groups of individuals. However, individuals from the endemic area had a significant accelerated aging when compared to individuals from São Paulo, a non-endemic area in Brazil. Moreover, the latter cohort was also epigenetically aged in relation to an Italian cohort. Our data shows that living in endemic areas for chronic infectious diseases results in remodelling of inflammaging and acceleration of epigenetic aging in individuals regardless of their infectious status. It also highlights that geographical, genetic and environmental factors influence aging and immunosenescence in their pace and profile.


Assuntos
Doenças Transmissíveis , Proteína Antagonista do Receptor de Interleucina 1 , Idoso , Envelhecimento/genética , Brasil/epidemiologia , Quimiocinas , Citocinas , Epigênese Genética , Humanos
2.
Horm Behav ; 130: 104952, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33647281

RESUMO

Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.


Assuntos
Captopril , Sódio , Animais , Captopril/farmacologia , Furosemida/farmacologia , Losartan/farmacologia , Masculino , Ratos , Ratos Endogâmicos SHR
3.
Benef Microbes ; 11(3): 255-268, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32264688

RESUMO

Food allergy is triggered when there is an abnormal activation of the immune system by food allergens. Currently, there is no curative therapy for this pathological condition. Due to the immunomodulatory properties of probiotics they are potential candidates as therapeutic tools for food allergy. Therefore, the aim of this study was to evaluate the probiotic effect of Saccharomyces cerevisiae UFMG A-905 (905) in an in vivo model of food allergy. Probiotic effect was assessed by clinical, histological, immunological and microbiological parameters analysis. Furthermore, we also evaluated if 905 after inactivation has an effect, as well as if such an effect is dose dependent. Our results showed that oral administration of only viable 905 promotes a significant attenuation of tissue injury and myeloperoxidase (MPO) activity levels. Moreover, the treatment reduced interleukin 17 levels, and administration of the supernatant from the yeast culture also promoted a significant decrease in MPO levels. However, considering the systemic parameters, immunoglobulin (Ig)E and IgG anti-ovalbumin, which are essentials for triggering the allergic process, there was no effect, suggesting that the yeast promotes a local but not a systemic effect in the model evaluated. In addition, we found that only high doses of viable 905 were able to attenuate the signs of inflammation. In conclusion, oral administration of 905 led to a local effect that depends on the viability of the yeast.


Assuntos
Hipersensibilidade Alimentar/prevenção & controle , Inflamação/prevenção & controle , Probióticos/administração & dosagem , Saccharomyces cerevisiae/fisiologia , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Viabilidade Microbiana , Peroxidase/metabolismo
4.
Mucosal Immunol ; 12(1): 188-199, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30279515

RESUMO

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-ß via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-ß)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.


Assuntos
Colite/imunologia , Neoplasias Colorretais/imunologia , Doenças Inflamatórias Intestinais/imunologia , Ácidos Linoleicos Conjugados/metabolismo , Macrófagos/imunologia , PPAR gama/metabolismo , Linfócitos T/imunologia , Ácido Aminossalicílico/metabolismo , Animais , Carcinogênese , Células Cultivadas , Colite/induzido quimicamente , Neoplasias Colorretais/induzido quimicamente , Sulfato de Dextrana , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR gama/genética , Fator de Crescimento Transformador beta/metabolismo
5.
Benef Microbes ; 9(3): 477-486, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29633632

RESUMO

The use of probiotics to prevent or treat mucosal inflammation has been studied; however, the combined effect of probiotics and prebiotics is unclear. The aim of this study was to test whether oral administration of a synbiotic (Simbioflora®) preparation containing Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis plus fructooligosaccharide could help control mucosal inflammation in experimental mucositis induced by 5-fluorouracil (5-FU). Male BALB/c mice were randomly divided into six groups: control (CTL), control + prebiotic (CTL+P), control + synbiotic (CTL+S), mucositis (MUC), mucositis + prebiotic (MUC+P), and mucositis + synbiotic (MUC+S). Mice from the CTL+S, MUC+S, CTL+P, and MUC+P groups received synbiotic or prebiotic daily by oral gavage for 13 days. Mice in the CTL and MUC groups received the same volume of saline. On day 11, mice in the MUC, MUC+P, and MUC+S groups received an intraperitoneal injection of 300 mg/kg 5-FU to induce mucositis. After 72 h, all mice were euthanised. Intestinal permeability, intestinal histology, and biochemical parameters were analysed. Group MUC showed a greater weight loss and increased intestinal permeability (0.020 counts per min [cpm]/g) compared to the CTL group (0.01 cpm/g) P<0.05. Both treatments attenuated weight loss compared to the MUC group. Nonetheless, the synbiotic caused a greater reduction in intestinal permeability (0.012 cpm/g) compared to the MUC (0.020 cpm/g) and MUC+P (0.016 cpm/g) groups P<0.05. Mice in groups MUC+P and MUC+S displayed significant recovery of lesions and maintenance of the mucus layer. There were no differences in the short-chain fatty acid concentrations in the faeces between the MUC and CTL groups (P>0.05). Increased acetate and propionate concentrations were evidenced in the faeces of the MUC+P and MUC+S groups. Only the synbiotic treatment increased the butyrate concentration (P<0.05). The results indicate that administration of synbiotic can decrease mucosal damage caused by mucositis.


Assuntos
Mucosite/prevenção & controle , Simbióticos/administração & dosagem , Administração Oral , Animais , Bifidobacterium animalis/crescimento & desenvolvimento , Bifidobacterium animalis/metabolismo , Peso Corporal , Ácidos Graxos Voláteis/análise , Fezes/química , Fluoruracila/administração & dosagem , Fluoruracila/toxicidade , Trato Gastrointestinal/patologia , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/metabolismo , Camundongos Endogâmicos BALB C , Mucosite/induzido quimicamente , Oligossacarídeos/administração & dosagem , Oligossacarídeos/metabolismo , Resultado do Tratamento
6.
Mar Environ Res ; 137: 8-15, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29500051

RESUMO

Fishes are currently facing novel types of anthropogenic stressors that have never experienced in their evolutionary history, such as ocean acidification. Under these stressful conditions, energetically costly processes, such as reproduction, may be sacrificed for increased chances of survival. This trade-off does not only affect the organism itself but may result in reduced offspring fitness. In the present study, the effects of exposure to high pCO2 levels were tested on the reproductive performance of a temperate species, the two-spotted goby, Gobiusculus flavescens. Breeding pairs were kept under control (∼600 µatm, pH∼ 8.05) and high pCO2 levels (∼2300 µatm, pH∼ 7.60) conditions for a 4-month period. Additionally, oxidative stress and energy metabolism-related biomarkers were measured. Results suggest that reproductive activity is stimulated under high pCO2 levels. Parental pairs in the simulated ocean acidification conditions exhibited increased reproductive output, with 50% more clutches and 44% more eggs per clutch than pairs under control conditions. However, there was an apparent trade-off between offspring number and size, as larvae of parental pairs under high pCO2 levels hatched significantly smaller, suggesting differences in parental provisioning, which could be related to the fact that these females produce more eggs. Moreover, results support the hypothesis of different energy allocation strategies used by females under high pCO2 conditions. These changes might, ultimately, affect individual fitness and population replenishment.


Assuntos
Dióxido de Carbono/análise , Recifes de Corais , Peixes/fisiologia , Água do Mar/química , Animais , Metabolismo Energético , Feminino , Larva , Estresse Oxidativo , Reprodução
7.
Mucosal Immunol ; 11(3): 820-834, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29346345

RESUMO

STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING-/- mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING-/- mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.


Assuntos
Colite/imunologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/imunologia , Intestinos/fisiologia , Linfócitos/imunologia , Proteínas de Membrana/metabolismo , Infecções por Salmonella/imunologia , Salmonella typhimurium/imunologia , Linfócitos T Reguladores/imunologia , Animais , Colite/induzido quimicamente , Colite/genética , Sulfato de Dextrana , Feminino , Fatores de Transcrição Forkhead/metabolismo , Homeostase , Imunidade Inata , Imunoglobulina A Secretora/sangue , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Salmonella/genética , Células Th1/imunologia
8.
Scand J Immunol ; 87(2): 73-79, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29193267

RESUMO

Oral tolerance is defined as a state of systemic hyporesponsiveness to an antigen that has been previously administered by the oral route. Many factors affect oral tolerance induction; some of them related to antigen, and some related to the animal. The age of the animal is one of the most important factors that affect oral tolerance as ageing brings many alterations in immune responses. Herein, we demonstrated that both the oral tolerance and pattern of immune reactivity triggered in early life were kept up to 15 months regarding the magnitude of antibody production, cell proliferation and cytokine profile when compared to immune responses induced in old mice. Therefore, our results corroborate with a promising proposal for prevaccination during childhood and young age, and a booster in older age, to make sure that the primary immunization in early life is not lost in aged individuals.


Assuntos
Antígenos/imunologia , Hipersensibilidade Tardia/imunologia , Tolerância Imunológica , Administração Oral , Animais , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Exposição Ambiental , Feminino , Humanos , Imunidade Humoral , Imunização , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Vacinas
9.
Horm Metab Res ; 47(9): 656-61, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25985323

RESUMO

DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively (χ(2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Carcinogênese/metabolismo , Receptor Nuclear Órfão DAX-1/metabolismo , Fator Esteroidogênico 1/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Adenoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/metabolismo , Adulto , Carcinogênese/genética , Criança , Pré-Escolar , Receptor Nuclear Órfão DAX-1/genética , Feminino , Expressão Gênica , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fator Esteroidogênico 1/genética
10.
J Fish Biol ; 85(3): 953-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25041317

RESUMO

Swimming abilities of wild-caught sand-smelt Atherina presbyter larvae were assessed as critical swimming speed (Ucrit ) throughout ontogeny. The mean Ucrit increased with size, ranging from 3·6 to 18·7 cm s(-1) , over the size range of 6·6-21·0 mm LT . This indicates that at hatching A. presbyter larvae, far from being passive floaters, are already capable of active behaviours, which may influence their dispersal patterns.


Assuntos
Osmeriformes/fisiologia , Natação , Distribuição Animal , Animais , Comportamento Animal , Larva
11.
Genet Mol Res ; 12(4): 6838-49, 2013 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-24391031

RESUMO

Differences in cellular and humoral immunity in Zebu (Bos taurus indicus) and European (B. taurus taurus) cattle breeds, which may be related to differences in resistance or susceptibility to infectious or parasitic diseases, are largely unknown. This study aimed to perform a comparative analysis of innate and adaptive immunity of European (including Holstein, Brown Swiss, and Hereford) and Zebu (including Gir, Nelore, and Guzera) breeds, by assessing their peripheral blood leukocyte profiles (i.e., monocytes, eosinophils, and lymphocytes, including CD4(+) and CD8(+) T cells, and CD21(+) B cells). Higher frequencies of cells involved in innate immunity were observed in Zebu breeds, particularly monocytes and non-T and non-B cells (13.37 ± 0.9058 and 37.67 ± 1.55, respectively). This finding may contribute to the increased resistance of B. taurus indicus to certain infectious and parasitic diseases. Considering other leukocyte populations in the peripheral blood, among-breed variation was greater than differences between the two subspecies. This study will serve as a basis for further investigations regarding comparative immunology and resistance to infectious and parasitic diseases of cattle.


Assuntos
Imunidade Adaptativa , Bovinos/imunologia , Imunidade Inata , Imunofenotipagem/veterinária , Animais , Linfócitos B/imunologia , Eosinófilos/imunologia , Feminino , Leucócitos/imunologia , Masculino , Monócitos/imunologia , Fenótipo , Linfócitos T/imunologia
12.
Drugs Today (Barc) ; 47(8): 575-81, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21850280

RESUMO

The combination of bupropion and naltrexone is one of the most promising new possibilities for the treatment of obesity in an era of increasing prevalence of this disease and decreasing options for its pharmacological management. Although approved by FDA panel members, it was temporally rejected by the FDA afterwards, who demanded more cardiovascular safety data for its commercialization. This monograph will focus on the physiology involved in its mechanisms of action and results of clinical trials.


Assuntos
Bupropiona/administração & dosagem , Naltrexona/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Bupropiona/farmacologia , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos , Naltrexona/farmacologia
13.
Scand J Immunol ; 73(1): 36-45, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21129001

RESUMO

The spleen is a secondary lymphoid organ that harbours a variety of cells such as T and B lymphocytes and antigen-presenting cells important to immune response development. In this study, we evaluated the impact of spleen removal in the immune response to experimental Trypanosoma cruzi infection. C57BL/6 mice were infected with Y strain of the parasite and infection was followed daily. Mice that underwent splenectomy had fewer parasites in peripheral blood at the peak of infection; however, mortality was increased. Histological analysis of heart and liver tissues revealed an increased number of parasites and inflammatory infiltrates at these sites. Spleen removal was associated with reduction in IFN-γ and TNF-α production during infection as well as with a decrease in specific antibody secretion. Haematological disorders were also detected. Splenectomized mice exhibited severe anaemia and decreased bone marrow cell numbers. Our results indicate that spleen integrity is critical in T. cruzi infection for the immune response against the parasite, as well as for the control of bone marrow haematological function.


Assuntos
Doença de Chagas/imunologia , Parasitemia/imunologia , Baço/imunologia , Trypanosoma cruzi/imunologia , Animais , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Coração/parasitologia , Histocitoquímica , Interferon gama/sangue , Fígado/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Parasitemia/mortalidade , Parasitemia/parasitologia , Baço/parasitologia , Baço/cirurgia , Esplenectomia , Fator de Necrose Tumoral alfa/sangue
14.
Scand J Immunol ; 71(4): 240-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20384867

RESUMO

Ageing is associated with several alterations in the immune system. Our aim in this study was to compare the development of immunity to Schistosoma mansoni infection in young versus aged C57Bl/6 mice using the liver as the main organ to evaluate pathological alterations and immune responses. In the acute phase, young mice had large liver granulomas with fibrosis and inflammatory cells. Chronic phase in young animals was associated with immunomodulation of granulomas that became reduced in size and cellular infiltrate. On the other hand, aged animals presented granulomas of smaller sizes already in the acute phase. Chronic infection in these mice was followed by no alteration in any of the inflammatory parameters in the liver. In concert with this finding, there was an increase in activated CD4+ T, CD19+ B and NK liver cells in young mice after infection whereas old mice had already higher frequencies of activated B, NK and CD4+ T liver cells and infection does not change these frequencies. After infection, liver production of inflammatory and regulatory cytokines such as IFN-gamma, IL-4 and IL-10 increased in young but not in old mice that had high levels of IL-4 and IL-10 regardless of their infection status. Our data suggest that the unspecific activation status of the immune system in aged mice impairs inflammatory as well as regulatory immune responses to S. mansoni infection in the liver, where major pathological alterations and immunity are at stage. This poor immune reactivity may have a beneficial impact on disease development.


Assuntos
Envelhecimento/imunologia , Hepatopatias/imunologia , Hepatopatias/patologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/patologia , Animais , Linfócitos B/imunologia , Separação Celular , Citocinas/biossíntese , Citocinas/imunologia , Citometria de Fluxo , Inflamação/imunologia , Inflamação/patologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia
15.
Scand J Immunol ; 70(3): 226-37, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19703012

RESUMO

Alcohol has a variety of short- and long-term effects on cell-mediated and humoral immune response. Herein, we have characterized the impact of high-dose EtOH administration on phenotypic and functional features of murine APC subsets, including dendritic cell (DC), macrophages and B cells. Impaired cytokine synthesis and Leishmania-phagocytosis was observed in peritoneal macrophages following EtOH administration. Moreover, EtOH exposure led to decreased levels of splenic myeloid DC and increased percentage of macrophages with no changes in splenic lymphoid DC and B cells. Adverse effects of short-term EtOH administration also resulted in impaired OVA-endocytosis by DC and macrophages. In contrast, EtOH consumption upregulates OVA-internalization by B cells. These changes on APC hierarchy may play a role shifting the fate of the immune response after EtOH ingestion. In addition to an overall downregulation of Toll-like receptor-TLR-4 expression by splenic APC, a downregulation of TLR-2 expression in macrophages was observed. Moreover, EtOH exposure altered the expression of co-signalling molecules on splenic APC, downregulating CD40 on macrophages and upregulating CD80 on B cells, with no impact on DC subsets. The net result of changes in TLR-mediated and co-stimulatory signals may determine the altered immunological status induced by acute consumption of alcohol. A direct impact of high-dose EtOH administration in the activation status of splenic CD4(+) T cells was observed. Together, our results demonstrated that short-term high-dose EtOH administration has differential impact on APC populations, downregulating splenic macrophages and DC activity but up-regulating B lymphocyte function as APC, and ultimately yielding a micro-environment that led to increased activation of CD4(+) T cells.


Assuntos
Apresentação de Antígeno/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Etanol/administração & dosagem , Macrófagos/imunologia , Animais , Apresentação de Antígeno/imunologia , Linfócitos B/efeitos dos fármacos , Antígeno B7-1/efeitos dos fármacos , Antígeno B7-1/imunologia , Antígeno B7-1/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD40/efeitos dos fármacos , Antígenos CD40/imunologia , Antígenos CD40/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Endocitose/efeitos dos fármacos , Endocitose/imunologia , Feminino , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo
16.
Cell Immunol ; 256(1-2): 1-5, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19233350

RESUMO

Senescence is characterized by several alterations in the immune system. Such modifications can be found in lymphoid organs as well as in the cellular components of the immune system. Several reports have suggested that immune dysfunction can affect both T and B cells, but T cells have been shown to be more susceptible to the effects of aging. B cell function may also be altered with reduction in germinal center formation, antibody response, and affinity maturation of antibodies. Herein we showed that although antigen-specific antibody response to a soluble antigen declines in 18-month old mice, total levels of serum antibodies as well as frequencies of spleen and bone marrow antibody-producing cells are increased in aged mice. In addition, proliferative response of non-stimulated spleen T cells from aged mice were augmented and insensitive to increasing doses of concanavalin A stimulation as compared to young mice that showed a typical dose-dependent response to mitogen stimulation in vitro. These data suggest that the higher activation mode of B and T cells in senescent mice is a result of an increased frequency of cells committed to previous antigenic experiences and with poor ability to respond to novel antigenic challenges.


Assuntos
Envelhecimento/imunologia , Linfócitos B/imunologia , Linfócitos T/imunologia , Animais , Afinidade de Anticorpos , Especificidade de Anticorpos , Antígenos/administração & dosagem , Células da Medula Óssea/imunologia , Feminino , Tolerância Imunológica , Imunoglobulinas/sangue , Técnicas In Vitro , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Baço/citologia , Baço/imunologia
17.
Clin Exp Immunol ; 154(3): 346-52, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19037919

RESUMO

There is common agreement that fibromyalgia (FM) is an extremely heterogeneous entity. Patients differ in their clinical symptoms, endocrine and immune parameters. In this study we evaluated endocrine and immunological features of distinct subsets of FM patients. In contrast to previous attempts to identify subsets of FM patients, based solely on their psychological and cognitive features, herein we propose to separate FM patients by genetic features. Allelic expression of the polymorphic promoter region of the serotonin transporter (5-HTTLPR) was analysed as a relevant genetic factor for FM. Seventy-five patients meeting the American College of Rheumatology criteria and 27 healthy age-matched controls participated in this study. All controls and FM patients were submitted to genotyping of 5-HTTLPR. Twenty-seven FM patients, who were able to discontinue hypnotic, sedative or psychotropic prescription medications for at least 2 weeks, were then subdivided into L (homozygote LL) or S groups (genotypes LS and SS). They were evaluated for salivary cortisol levels, absolute number of leucocyte subpopulations, including natural killer (NK) cells and activated T and B lymphocytes. Both groups presented decreased cortisol levels, more intense in the L group, increased all B lymphocytes subsets and reduced CD4+CD25high T lymphocytes. The L group had increased CD4+CD25low activated T lymphocytes, while the S group displayed elevated CD4+ human leucocyte antigen D-related (HLA-DR)+ activated T lymphocytes and decreased NK cells. We demonstrate that genetic factors may help to identify FM individuals with differentially altered frequencies of immune cells.


Assuntos
Fibromialgia/genética , Fibromialgia/imunologia , Adulto , Subpopulações de Linfócitos B/imunologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Hidrocortisona/metabolismo , Células Matadoras Naturais/imunologia , Contagem de Leucócitos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Saliva/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Subpopulações de Linfócitos T/imunologia
18.
Scand J Immunol ; 68(3): 306-14, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18782259

RESUMO

Herein, we described an experimental model of high-dose ethanol (EtOH) administration, able to induce in vitro impairment in macrophage phagocytic capacity, already observed at 24 h after the last EtOH administration. This phenomenon was characterized by enlarged time required for adhesion and internalization events. Parallel studies documented an overall impaired production of interleukin (IL)-6 and nitric oxide (NO) production by peritoneal macrophages in EtOH-treated mice following interferon (IFN)-gamma and lipopolysaccharide (LPS) stimuli. Although the impaired IL-6 response could not be restored by any of the experimental conditions tested, the lower NO response to INF-gamma and LPS was overturned by simultaneous IFN-gamma/LPS stimuli. It was interesting to notice that high-dose EtOH administration drives peritoneal macrophages towards long-term impairment in phagocytosis capacity with slower adhesion time, but with no impact on the time required for internalization. Moreover, 30 days after the last EtOH administration, lower IL-6 response to INF-gamma and impaired NO production were still observed in response to IFN-gamma/LPS stimuli, with the IL-6 response to IFN-gamma being restored by IFN-gamma/LPS stimuli. Histological studies showed that high-dose EtOH administration led to long-term in vivo impairment of antigen-clearance following OVA-driven delayed-type-hypersensitivity induction, characterized by the presence of a large amount of unprocessed OVA surrounded by dermal inflammatory infiltrate, suggesting defective activity of antigen-presenting cells. Together, these findings supported our hypothesis that the poor antigen clearance in vivo may be related to the impaired macrophage function in vitro. These observations in the murine experimental model may reflect some of the consequences of EtOH consumption by humans.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Etanol , Macrófagos Peritoneais/imunologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Animais , Células Apresentadoras de Antígenos/imunologia , Células Cultivadas , Relação Dose-Resposta Imunológica , Etanol/sangue , Feminino , Interferon gama/farmacologia , Interleucina-6/biossíntese , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/biossíntese , Fagocitose/efeitos dos fármacos , Fatores de Tempo
19.
Scand J Immunol ; 68(5): 516-25, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18803607

RESUMO

Herein we have employed an alternative strategy to assess the cytokine patterns of circulating leukocytes and correlate dominant cytokine profiles with indeterminate-IND and cardiac-CARD clinical forms of Chagas disease. We have first calculated median percentages of cytokine-positive leukocytes of our study sample to establish, for each cytokine-positive cell population, the cut-off edge that would segregate 'low' and 'high' cytokine producers to build colour diagrams and draw a panoramic cytokine chart. Using this approach we demonstrated that most IND individuals presented a dominant regulatory cytokine profile, whereas CARD individuals displayed a dominant inflammatory cytokine pattern. In addition, radar chart analysis confirmed the dichotomic cytokine balance between IND and CARD groups and further allowed the identification of the relative contribution of each cell population for the global cytokine pattern. Data analysis demonstrated that CD4+ T cells were the major cell population defining the regulatory profile in IND, whereas monocytes and CD4+ T cells determined the inflammatory cytokine pattern in CARD individuals. Interestingly, in vitro stimulation with trypomastigote Trypanosoma cruzi antigen was able to invert the cytokine balances in IND and CARD groups. Upon antigenic stimulation, changes in the frequencies of IL-10-producing CD4+ T cells and monocytes drove IND individuals towards an inflammatory pattern and CARD towards a regulatory cytokine profile. A similar inversion could be found after in vivo treatment of IND and CARD individuals with benzonidazole. Altogether, these findings shed some light into the complex cytokine network underlying the immunopathogenesis of Chagas disease and provide putative immunological biomarkers of disease severity and therapeutic response.


Assuntos
Cardiomiopatia Chagásica/imunologia , Doença de Chagas/imunologia , Citocinas/sangue , Leucócitos Mononucleares/imunologia , Trypanosoma cruzi/imunologia , Adulto , Idoso , Animais , Antígenos de Protozoários/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/tratamento farmacológico , Doença de Chagas/sangue , Doença de Chagas/tratamento farmacológico , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Nitroimidazóis/farmacologia , Nitroimidazóis/uso terapêutico , Linfócitos T/citologia , Linfócitos T/imunologia , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico
20.
Cell Immunol ; 254(1): 63-73, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18707680

RESUMO

Oral administration of protein antigens, such as ovalbumin, may result in induction of either tolerance or immunization. To avoid oral tolerance, there are new strategies to protect the antigens from degradation within the gastrointestinal tract and to allow them to reach inductive immunological sites. One such strategy is the usage of liposomes. Different parameters may influence the stability of liposomes in the gastrointestinal tract. Herein, we studied the immunological consequences of oral administration of liposome-encapsulated ovalbumin in different strains of mice using different liposomes. Our data demonstrated that ovalbumin liposomes improved the induction of oral immunization and the degree of improvement depended on the liposome type and on the strain of mice used. The mechanism responsible for this differential effect of liposomes depended on the site of antigen release and absorption. Therefore, some liposomes might be suitable as adjuvants for oral immunization, others for oral tolerance induction.


Assuntos
Tolerância Imunológica , Lipossomos/química , Ovalbumina/administração & dosagem , Vacinação/métodos , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Imunidade nas Mucosas/imunologia , Imunoglobulina A/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lipossomos/administração & dosagem , Camundongos , Ovalbumina/imunologia
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