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1.
Life Sci ; 242: 117220, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881230

RESUMO

BACKGROUND/AIMS: Previous studies have demonstrated that Galactooligosaccharides (GOS), known as "bifidus factor", has anti-inflammatory effects. Colitis, a kind of colonic inflammatory damage could be induced by different chemicals. The pathogenesis and mechanism of colitis remains unclear, and may be related to intestinal microflora, genetic susceptibility or immune factors. The aim is to explore the effects of GOS on intestinal flora and its anti-inflammatory effects in Dextran Sulfate Sodium (DSS) induced murine colitis and extrapolate the underlying mechanism. MAIN METHODS: Initially, 5% DSS was used to induced colitis by free access to drinking water for 5-7 days. Then the mice were treated with GOS 1 day after DSS treatment. Colon samples were evaluated grossly using a microscope. The percentage of Treg and Th17 cells was analyzed by flow cytometry. The levels of cytokines secretion and mRNA expression were detected by ELISA and real-time PCR. The level of protein was detected by western blot. KEY FINDINGS: GOS attenuated DSS induced body weight loss and also reduced the increase in disease index caused by DSS. GOS ameliorated DSS induced colonic histological damage. The protective effect of GOS on DSS induced colitis may be partly attributed to intestinal flora regulation and Th17/Treg imbalance. Furthermore, GOS markedly decreased cytokines (IL-6, IL-18, IL-13 and IL-33) secretion and mRNA expression in colon tissues, through inhibiting activation of NF-κB pathways. SIGNIFICANCE: GOS could prevent the DSS induced colitis through intestinal flora regulation and reduce the secretion of inflammation related cytokines relying on the NF-κB signaling pathway.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , NF-kappa B/metabolismo , Oligossacarídeos/uso terapêutico , Panteteína/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Colite/induzido quimicamente , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Microbioma Gastrointestinal/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Panteteína/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos
2.
J Dairy Sci ; 102(11): 9570-9585, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477303

RESUMO

Colitis severely affects the quality of life of patients, and lactic acid bacteria have been reported to be able to improve or treat colitis. In this study, we selected a strain of Lactobacillus fermentum (CQPC04) with good resistance in vitro to evaluate its effect on improvement in mice with dextran sulfate sodium (DSS)-induced colitis. We analyzed the effects of L. fermentum CQPC04 on mice with colitis macroscopically via colon length and histopathology. We also used conventional biochemical and ELISA kits, real-time quantitative PCR (RT-qPCR), and Western blotting to analyze microscopically the effects of L. fermentum CQPC04 on related oxidant indices and pro- and anti-inflammatory cytokines in serum and colon tissue of mice. The results indicated that L. fermentum CQPC04 notably increased colon length and ameliorated pathological damage of colon tissue in colitic mice. Serum indices showed that L. fermentum CQPC04 increased the enzyme activity of total superoxide dismutase (T-SOD) and catalase (CAT) and decreased the content of malondialdehyde (MDA) and the activity of myeloperoxidase (MPO). In addition, it inhibited the release of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IFN-γ, IL-1ß, IL-6, and IL-12, and increased the release of the anti-inflammatory cytokine IL-10 in serum. The RT-qPCR experiments confirmed that L. fermentum CQPC04 downregulated the expression of pro-inflammatory cytokine nuclear factor-κB-p65 (NF-κBp65), NF-κB inhibitor-α (IκB-α), TNF-α, IFN-γ, IL-1ß, IL-6, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS), and upregulated the expression of IL-10 in colon tissue. Western blot analysis indicated that L. fermentum CQPC04 significantly reduced expression of NF-κBp65, TNF-α, IL-1ß, COX-2, and iNOS in mouse colon tissues, and increased expression of IκB-α and superoxide dismutase 2 (SOD2). Thus, L. fermentum CQPC04 could effectively alleviate the symptoms of DSS-induced colitis mice and is a potential probiotic for human experiments.


Assuntos
Colite/dietoterapia , Lactobacillus fermentum , NF-kappa B/metabolismo , Probióticos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colite/prevenção & controle , Citocinas/sangue , Sulfato de Dextrana , Feminino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/metabolismo , Substâncias Protetoras , Fator de Necrose Tumoral alfa/metabolismo
3.
Nutrients ; 11(8)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370166

RESUMO

Iron is an essential nutrient needed for physiological functions, particularly during the developmental period of the early childhood of at-risk populations. The purpose of this study was to investigate, in an experimental colitis, the consequences of daily oral iron ingestion in the early period on the inflammatory response, the spleen T helper (Th) profiles and the associated molecular mechanisms. Juvenile mice orally received microencapsulated ferric iron or water for 6 weeks. On adult mice, we induced a sham or experimental trinitrobenzene sulfonic acid (TNBS) moderate colitis during the last week of the experiment before sacrificing the animals 7 days later. The severity of the gut inflammation was assessed by macroscopic damage scores (MDS) and the myeloperoxidase activity (MPO). Th profiles were evaluated by the examination of the splenic gene expression of key transcription factors of the Th differentiation (Tbet, Gata3, Foxp3 and RORγ) and the methylation of their respective promoter. While TNBS-induced colitis was associated with a change of the Th profile (notably an increase in the Tbet/Gata3 ratio in the spleen), the colitis-inhibition induced by ferric iron was associated with a limitation of the splenic Th profiles perturbation. The inhibition of the splenic Tbet gene overexpression was associated with an inhibition of promoter hypomethylation. In summary, mice treated by long-term oral ferric iron in the early period of life exhibited an inhibition of colitis associated with the inhibition of the splenic Tbet promoter hypomethylation and gene overexpression.


Assuntos
Colite/prevenção & controle , Compostos Férricos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regiões Promotoras Genéticas/fisiologia , Fatores de Transcrição/metabolismo , Administração Oral , Adulto , Envelhecimento , Animais , Ilhas de CpG , Composição de Medicamentos , Compostos Férricos/administração & dosagem , Humanos , Masculino , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Transcrição/genética
4.
Nutrients ; 11(8)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362373

RESUMO

BACKGROUND: In this study, we investigate the impact of epigallocatechin gallate (EGCG), the most abundant and potent catechin in green tea, on a mouse model of inflammatory bowel disease (IBD) and the underlying mechanisms of action. METHODS: C57BL/6J mice were subjected to dextran sulfate sodium (DSS)-induced IBD-like disease and then randomly divided into three groups: Model group (MD), low-dose EGCG group (LE, 20 mg/kg/d), and high-dose EGCG group (HE, 50 mg/kg/d). DSS-induced clinical and macroscopic changes were monitored daily. Intestinal permeability was assessed by FITC-Dextran assay. RESULTS: Both high- and low-dose EGCG treatment alleviated clinical manifestations including body weight loss and disease activity index (DAI) of DSS-induced colitis. The DAI score was significantly improved after two days of EGCG treatment. At the end of the study, the macroscopic severity score (MSS) of HE and LE treatment groups were 2.4 ± 1.2, and 2.2 ± 1.0, respectively, significantly lower than that of the controls (5.0 ± 2.1). EGCG treatment also prevented colon shortening, and improved intestinal permeability and histopathological changes. In addition, EGCG treatment attenuated colon inflammation by suppressing colonic levels of pro-inflammatory cytokines IL-6, MCP-1, and TNF-alpha, and inhibited CD3+ T cell and CD68+ macrophage infiltration. CONCLUSION: EGCG is effective in inflammatory colitis because it reduces cellular and molecular inflammation, and reduces intestinal permeability.


Assuntos
Anti-Inflamatórios/administração & dosagem , Catequina/análogos & derivados , Colite/prevenção & controle , Colo/efeitos dos fármacos , Citocinas/metabolismo , Fármacos Gastrointestinais/administração & dosagem , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Animais , Catequina/administração & dosagem , Colite/imunologia , Colite/metabolismo , Colite/patologia , Colo/imunologia , Colo/metabolismo , Colo/patologia , Citocinas/imunologia , Sulfato de Dextrana , Modelos Animais de Doenças , Mediadores da Inflamação/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Permeabilidade , Linfócitos T/imunologia , Linfócitos T/metabolismo
5.
Nutrients ; 11(8)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362418

RESUMO

Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are chronic disorders of the gastrointestinal tract, although the exact causes of IBD remain unknown. Present treatments for IBDs have poor tolerability and insufficient therapeutic efficacy, thus, alternative therapeutic approaches are required. Soybean-derived isoflavones have multiple bioactivities such as anti-inflammation. However, the low water solubility of soybean isoflavones limits their bioavailability and practical use. Therefore, in order to study the preventive effects of water-soluble soybean isoflavones on colonic inflammatory status, we examined soybean-derived isoflavone glycosides (SIFs) in a dextran sodium sulfate (DSS)-induced murine colitis model and in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Oral administration of SIF (0.5 w/v%) attenuated DSS-induced colitis in terms of body weight decrease, colon shortening, epithelial apoptosis, histological score, mRNA levels of inflammatory cytokines, and immune cell infiltration in colon tissues. In the in vitro assessment, we observed the inhibitory effects of SIF on the production of nitric oxide and prostaglandin E2, via suppression of inducible nitric oxide synthase and cyclooxygenase-2 expression in RAW264.7 macrophages in response to LPS. Furthermore, we confirmed that the expression of inflammatory cytokines and chemokines were decreased by pre-treatment with SIF in LPS-activated RAW264.7 macrophages. Moreover, we demonstrated that SIF suppressed inflammatory mediators involved in nuclear factor-κB signaling pathway via inhibitory κB kinase phosphorylation and degradation of inhibitory κB. Our results suggested that SIF may be beneficial for the remission of colonic inflammatory status including IBDs.


Assuntos
Anti-Inflamatórios/administração & dosagem , Colite/prevenção & controle , Colo/efeitos dos fármacos , Sulfato de Dextrana , Isoflavonas/administração & dosagem , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Soja , Animais , Anti-Inflamatórios/isolamento & purificação , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/imunologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Isoflavonas/isolamento & purificação , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Células RAW 264.7 , Indução de Remissão , Transdução de Sinais , Soja/química
6.
J Dairy Sci ; 102(8): 6718-6725, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31155246

RESUMO

This study aimed to screen lactic acid bacteria (LAB) for their anti-inflammatory activity by using RAW264.7 cells and dextran sulfate sodium (DSS)-induced colitis. In all, 192 LAB strains were isolated from healthy human feces, of which 8 strains showed excellent nitric oxide (NO) inhibitory activity. Peptidoglycan extracts of these 8 LAB strains were subjected to NO assay, Western blot, and ELISA. Among the 8 tested strains, extracts of 4 strains significantly inhibited the production of NO, related enzyme activities such as inducible nitric oxide synthase and cyclooxygenase 2, and key cytokines such as tumor necrosis factor-α and IL-6 in RAW264.7 cells. The 4 strains belonged to Lactobacillus (CAU1054, CAU1055, CAU1064, and CAU1301). Oral administration of the 4 strains inhibited DSS-induced body weight loss, colon shortening, and colon damage in ICR mice. The colon tissue of the mice treated with Lactobacillus plantarum strain CAU1055 had significantly reduced levels of inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor-α, and IL-6. We found that strain CAU1055 could be used as a candidate probiotic strain for the prevention and treatment of inflammatory bowel disease. Further studies are warranted to confirm the mechanisms of interaction between peptidoglycan of L. plantarum strain CAU1055 and upstream cellular signaling mediators.


Assuntos
Colite/prevenção & controle , Sulfato de Dextrana/farmacologia , Inflamação/prevenção & controle , Lactobacillus plantarum/fisiologia , Lipopolissacarídeos/farmacologia , Animais , Colite/induzido quimicamente , Colite/terapia , Inibidores de Ciclo-Oxigenase 2 , Citocinas/antagonistas & inibidores , Modelos Animais de Doenças , Fezes/microbiologia , Humanos , Inflamação/terapia , Lactobacillus plantarum/isolamento & purificação , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Probióticos/administração & dosagem , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
7.
Gac Med Mex ; 155(Suppl 1): S32-S37, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31182876

RESUMO

Introduction: In Mexico, seroprevalence of Entamoeba histolytica is 8.4%. The intestinal amebiasis in patients with acute leukemia of novo, after the start of chemotherapy (CT) in the Hematology Service of the CMN 20 de Noviembre is 12%, even if patients show a negative baseline coprological test. Objective: To find out if the administration of tinidazole, in patients with acute leukemia and negative coprological test, at the beginning of the CT, decreases the incidence of amoebic colitis during the induction to remission. Method: Prospective and not comparative study. Patients with de novo diagnosis of acute leukemia who initiate induction and initial coprological CT. Tinidazole was indicated, 2 g/day for 5 days in the first week of CT started. They were monitored until the induction was concluded and hematopoietic recovery started. Results: 38 patients, 15 women and 23 men with a mean age of 44 years (16-72), with acute lymphoblastic leukemia 19, myeloblastic 16 and promyelocytic 3. Cases without and with intestinal amebiasis were 35 and 3, respectively. Patients with amebiasis only received tinidazole for 3 days and it was given 2 days after the CT started. Conclusion: Tinidazole, in patients with acute de novo leukemia who initiate induction CT, is effective in the prevention of intestinal amebiasis, during the induction stage, if administered at 2 g/day, for five days, starting on day 1 of the CT.


Assuntos
Colite/prevenção & controle , Colite/parasitologia , Disenteria Amebiana/prevenção & controle , Tinidazol/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Colite/complicações , Disenteria Amebiana/complicações , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
8.
Eur J Pharmacol ; 857: 172453, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202807

RESUMO

Aesculin, a natural product from the traditional and widely-used Chinese medicine named Cortex fraxini, has attracted attention as a novel therapeutic modulator of inflammation. However, little is known about its effect on ulcerative colitis (UC). This study aimed to investigate the protective effects and mechanisms of aesculin on colitis. The results showed that, few cytotoxicity of aesculin were shown in vivo and in the RAW264.7 macrophages, while aesculin significantly relieved the symptoms of DSS-induced colitis and restrained the expression of inflammatory factors including iNOS, IL-1ß, TNF-α in both peritoneal macrophages and colonic tissues from DSS-induced mice and RAW264.7 macrophages. Of note, aesculin attenuated the activity of NF-κB signaling while promoted the nuclear localization of PPAR-γ in both rectal tissues from DSS-induced mice and LPS-stimulated macrophages. These findings demonstrated that the protection of aesculin against ulcerative colitis might be due to its regulation on the PPAR-γ and NF-κB pathway. Thus, aesculin could serve as a potential therapeutic agent for the treatment of ulcerative colitis.


Assuntos
Colite/metabolismo , Colite/prevenção & controle , Sulfato de Dextrana/efeitos adversos , Esculina/farmacologia , NF-kappa B/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Colite/induzido quimicamente , Colite/patologia , Citocinas/biossíntese , Citoproteção/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Células RAW 264.7
9.
Immunology ; 158(1): 19-34, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31215020

RESUMO

Studies with gene-deficient and gnotobiotic mice have identified many host and microbial factors that contribute to induced colitis, but information on whether specific factors determine susceptibility under more physiological conditions is lacking. Using wild-type strains that differ in their IgA response but harbor a diverse gut microbiome, we found that the IgA-high strain CBA/CaJ (CBA) is resistant to acute colitis induced with dextran sodium sulfate (DSS), unlike the IgA-low strain C57BL/6 (B6). Resistance was associated with extensive IgA-coating of fecal bacteria, lower fecal bacterial loads and greater abundance of barrier-protective transcripts in colonic tissues under homeostatic conditions. Fecal microbial transplant (FT) experiments revealed that disease induction in B6 mice was associated with a cohort of bacteria that are not targeted by IgA. However, CBA mice continued to be resistant to colitis induction following FTs from B6 mice, indicating that they are able to contain such colitogenic members. In support of a role for bacterial exclusion in resistance, oral administration of immunoglobulins decreased DSS-induced disease in B6 mice. In F1 mice derived separately with CBA and B6 dams and in F1 mice backcrossed to the two parental strains, resistance segregated with the IgA response of the pups and not with barrier-associated transcripts or bacterial loads. Interestingly, B6 pups foster-nursed on CBA dams continued to be susceptible in later life, whereas CBA pups foster-nursed on B6 dams continued to be resistant. Together, the data indicate that a high-IgA response in adult life can protect against colitis and compensate for IgA deficiency in early life.


Assuntos
Bactérias/imunologia , Colite/prevenção & controle , Colo/microbiologia , Sulfato de Dextrana , Microbioma Gastrointestinal/imunologia , Imunoglobulina A/imunologia , Animais , Animais Recém-Nascidos , Carga Bacteriana , Colite/induzido quimicamente , Colite/imunologia , Colite/microbiologia , Colo/imunologia , Colo/metabolismo , Cruzamentos Genéticos , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Imunoglobulina A/metabolismo , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Lactação , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Permeabilidade , Gravidez , Especificidade da Espécie
10.
Cells ; 8(6)2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212833

RESUMO

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn's disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn's disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.


Assuntos
Anti-Inflamatórios/uso terapêutico , Microbioma Gastrointestinal , Glutationa Transferase/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colite/induzido quimicamente , Colite/microbiologia , Colite/prevenção & controle , Colite/terapia , Doença de Crohn/microbiologia , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Humanos , Imunização , Imunomodulação , Camundongos Endogâmicos BALB C , Fenótipo , Ácido Trinitrobenzenossulfônico
11.
Acta Cir Bras ; 34(4): e201900406, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31038584

RESUMO

PURPOSE: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. METHODS: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. RESULTS: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. CONCLUSION: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Colo/efeitos dos fármacos , Enema/métodos , Mucosa Intestinal/efeitos dos fármacos , Mesalamina/farmacologia , Mucinas/análise , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite/patologia , Colite/prevenção & controle , Colo/metabolismo , Colo/patologia , Colostomia , Fezes , Trânsito Gastrointestinal , Histocitoquímica , Processamento de Imagem Assistida por Computador , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Mesalamina/uso terapêutico , Mucinas/efeitos dos fármacos , Estresse Oxidativo , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
12.
Infect Immun ; 87(8)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31138616

RESUMO

Infection with parasite helminths induces potent modulation of the immune system of the host. Epidemiological and animal studies have shown that helminth infections can suppress or exacerbate unrelated autoimmune, allergic, and other inflammatory disorders. There is growing evidence that helminth infection-mediated suppression of bystander inflammatory responses is influenced by alterations in the intestinal microbiome modulating metabolic and immune functions of the infected host. We analyzed the fecal microbiota of mice infected with adult male Schistosoma mansoni worms, which are less susceptible to experimental colitis, and male- and female-worm-infected mice, which are highly sensitive to colitis. While both groups of infected mice developed a disrupted microbiota, there were marked alterations in mice with male and female worm infections. Antibiotic-treated recipients that were cohoused with both types of S. mansoni worm-infected mice acquired a colitogenic microbiome, leading to increased susceptibility to experimental colitis. Following anthelmintic treatment to remove worms from worm-only-infected mice, the mice developed exacerbated colitis. This study provides evidence that adult male S. mansoni worm infection modulates the host's immune system and suppresses bystander colitis while limiting dysbiosis of the host's intestinal microbiome during infection.


Assuntos
Colite/prevenção & controle , Microbioma Gastrointestinal , Esquistossomose mansoni/imunologia , Animais , Suscetibilidade a Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Esquistossomose mansoni/microbiologia
13.
J Med Food ; 22(7): 672-679, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112045

RESUMO

Dietary products may protect against inflammatory bowel disease (IBD) through mechanisms such as forming gut microbiota structures and providing substrates for microbial metabolism. Recently, many studies have been conducted on diets that potentially alleviate or suppress IBD development. To assess the efficacy of dietary oils in treating IBD, we examined the protective effects of olive oil, coconut oil, corn oil, and cottonseed oil in a dextran sodium sulfate (DSS)-induced colitis mouse model. Treatment with cottonseed oil or corn oil ameliorated the severity of DSS-induced colitis, alleviating weight loss and preventing the shortening of the intestine. Moreover, cottonseed oil or corn oil treatment significantly reduced the expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-17, as well as the expression of oxidative stress markers, including 8-hydroxyguanosine and nitrotyrosine in colon sections, compared with vehicle treatment. Cottonseed oil treatment inhibited intestinal fibrosis by reducing the expression of α-smooth muscle actin and type I collagen, compared with vehicle treatment in mice with DSS-induced colitis. Cottonseed oil protects against intestinal inflammation and the development of intestinal fibrosis by reducing inflammatory cytokines and oxidative stress markers, and may therefore be useful as a dietary product with therapeutic benefits for IBD.


Assuntos
Colite/prevenção & controle , Óleo de Sementes de Algodão/administração & dosagem , Substâncias Protetoras/administração & dosagem , Actinas/genética , Actinas/imunologia , Animais , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Colágeno Tipo I/genética , Colágeno Tipo I/imunologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sulfatos/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
14.
Psychopharmacology (Berl) ; 236(5): 1653-1670, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31119329

RESUMO

RATIONALE: Mycobacterium vaccae (NCTC 11659) is an environmental saprophytic bacterium with anti-inflammatory, immunoregulatory, and stress resilience properties. Previous studies have shown that whole, heat-killed preparations of M. vaccae prevent allergic airway inflammation in a murine model of allergic asthma. Recent studies also demonstrate that immunization with M. vaccae prevents stress-induced exaggeration of proinflammatory cytokine secretion from mesenteric lymph node cells stimulated ex vivo, prevents stress-induced exaggeration of chemically induced colitis in a model of inflammatory bowel disease, and prevents stress-induced anxiety-like defensive behavioral responses. Furthermore, immunization with M. vaccae induces anti-inflammatory responses in the brain and prevents stress-induced exaggeration of microglial priming. However, the molecular mechanisms underlying anti-inflammatory effects of M. vaccae are not known. OBJECTIVES: Our objective was to identify and characterize novel anti-inflammatory molecules from M. vaccae NCTC 11659. METHODS: We have purified and identified a unique anti-inflammatory triglyceride, 1,2,3-tri [Z-10-hexadecenoyl] glycerol, from M. vaccae and evaluated its effects in freshly isolated murine peritoneal macrophages. RESULTS: The free fatty acid form of 1,2,3-tri [Z-10-hexadecenoyl] glycerol, 10(Z)-hexadecenoic acid, decreased lipopolysaccharide-stimulated secretion of the proinflammatory cytokine IL-6 ex vivo. Meanwhile, next-generation RNA sequencing revealed that pretreatment with 10(Z)-hexadecenoic acid upregulated genes associated with peroxisome proliferator-activated receptor alpha (PPARα) signaling in lipopolysaccharide-stimulated macrophages, in association with a broad transcriptional repression of inflammatory markers. We confirmed using luciferase-based transfection assays that 10(Z)-hexadecenoic acid activated PPARα signaling, but not PPARγ, PPARδ, or retinoic acid receptor (RAR) α signaling. The effects of 10(Z)-hexadecenoic acid on lipopolysaccharide-stimulated secretion of IL-6 were prevented by PPARα antagonists and absent in PPARα-deficient mice. CONCLUSION: Future studies should evaluate the effects of 10(Z)-hexadecenoic acid on stress-induced exaggeration of peripheral inflammatory signaling, central neuroinflammatory signaling, and anxiety- and fear-related defensive behavioral responses.


Assuntos
Anti-Inflamatórios/imunologia , Anti-Inflamatórios/isolamento & purificação , Mycobacterium/imunologia , Mycobacterium/isolamento & purificação , Estresse Psicológico/imunologia , Estresse Psicológico/prevenção & controle , Animais , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/prevenção & controle , Colite/induzido quimicamente , Colite/imunologia , Colite/prevenção & controle , Medo/efeitos dos fármacos , Medo/fisiologia , Inflamação/imunologia , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/imunologia , Microbiologia do Solo , Estresse Psicológico/induzido quimicamente
15.
Med Hypotheses ; 127: 66-70, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31088651

RESUMO

Immune checkpoint inhibitor (ICPi) therapy has transformed the way we treat cancer. However, its immune related adverse events (irAEs) can be debilitating and life threatening. Immune therapy-induced diarrhea (ITID) is one of the most commonly encountered irAEs and can lead to expensive and prolonged hospitalizations. The current standard of care for grade 3 or 4 ITID involves ICPi discontinuation, the initiation of steroids, and infliximab for refractory disease. This treatment regimen reverses the desired anti-tumor effect of ICPis, can lead to side effects, and is cost-ineffective. We report the first case of the successful treatment of grade 3 ITID with steroids and an amino acid-based oral rehydration solution (AA-ORS), enterade. Research suggests that AA-ORS may be used to reduce diarrhea and adequately hydrate patients, in contrast to glucose-based oral rehydration solutions, which have been implicated as a contributing factor to diarrhea in cancer patients. We hypothesize that an AA-ORS may mitigate ITID via safer and more economically viable means than the current standard of care, but more controlled trials are needed to test this hypothesis.


Assuntos
Antineoplásicos/efeitos adversos , Diarreia/induzido quimicamente , Neoplasias/tratamento farmacológico , Soluções para Reidratação/administração & dosagem , Administração Oral , Aminoácidos , Antineoplásicos/uso terapêutico , Bicarbonatos/administração & dosagem , Ensaios Clínicos como Assunto , Colite/imunologia , Colite/prevenção & controle , Feminino , Glucose/administração & dosagem , Humanos , Imunoterapia , Pessoa de Meia-Idade , Cloreto de Potássio/administração & dosagem , Guias de Prática Clínica como Assunto , Cloreto de Sódio/administração & dosagem , Esteroides/uso terapêutico
16.
Nutrients ; 11(5)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137456

RESUMO

Walnuts contain a complex array of natural compounds and phytochemicals that exhibit a wide range of health benefits, including protection against inflammation and colon cancer. In this study, we assess the effects of dietary supplementation with walnuts on colonic mucosal injury induced in mice by the ulcerogenic agent, dextran sodium sulfate (DSS). C57Bl/6J mice were started on the Total Western Diet supplemented with freshly-ground whole walnuts (0, 3.5, 7 and 14% g/kg) 2 weeks prior to a 5-day DSS treatment and walnut diets were continued throughout the entire experimental period. Mice were examined at 2 days or 10 days after withdrawal of DSS. In a separate study, a discovery-based metabolite profiling analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on fecal samples and colonic mucosa following two weeks of walnut supplementation. Dietary walnut supplementation showed significant effects in the 10-day post-DSS recovery-phase study, in which the extent of ulceration was significantly reduced (7.5% vs. 0.3%, p < 0.05) with 14% walnuts. In the metabolite-profiling analysis, walnuts caused a significant increase in several polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and 9-oxo-10(E),12(E)-octadecadienoic acid (9-oxoODA), as well as kynurenic acid. In colon tissue samples, walnuts caused a significant increase in the levels of S-adenosylhomocysteine (SAH) and betaine, important components of fatty acid ß-oxidation. These metabolite changes may contribute in part to the observed protection against DSS-induced inflammatory tissue injury.


Assuntos
Ração Animal , Colite/prevenção & controle , Colo/metabolismo , Sulfato de Dextrana , Suplementos Nutricionais , Mucosa Intestinal/metabolismo , Juglans , Nozes , Animais , Cromatografia Líquida de Alta Pressão , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/patologia , Modelos Animais de Doenças , Fezes/química , Mucosa Intestinal/patologia , Metabolômica/métodos , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem
17.
Eur J Pharmacol ; 856: 172403, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31128093

RESUMO

Our aim was to examine the effects of ASB17061, an orally active novel chymase inhibitor, on angiotensin II-induced abdominal aortic aneurysm (AAA) in apolipoprotein E-deficient mice. Oral administration of ASB17061 (10 mg/kg) significantly suppressed angiotensin II-induced AAA formation in these mice. The pro-matrix metalloproteinase-9 (pro-MMP-9) level in AAA lesions was significantly suppressed by ASB17061 treatment, indicating that ASB17061 inhibited the accumulation of pro-MMP-9-producing cells in AAA lesions. Mouse mast cell protease 4 (mMCP-4, human chymase ortholog) was injected into BALB/c mice intraperitoneally to examine the ability of mMCP-4 to induce the accumulation of pro-MMP-9-producing cells. An intraperitoneal injection of mMCP-4 induced the accumulation of pro-MMP-9-producing cells including CD11b + Gr-1 + cells. Taken together, these data indicate that ASB17061 is a promising novel oral therapeutic agent for human AAA.


Assuntos
Angiotensina II/farmacologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/prevenção & controle , Apolipoproteínas E/deficiência , Ácido Benzoico/farmacologia , Quimases/antagonistas & inibidores , Inibidores de Serino Proteinase/farmacologia , Animais , Aneurisma da Aorta Abdominal/metabolismo , Colite/prevenção & controle , Precursores Enzimáticos/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C
18.
Nutrients ; 11(4)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987344

RESUMO

Intestinal bifidobacteria benefit human health by promoting and modulating the gut flora, and boosting therapeutic efficiency for chronic metabolic diseases and cancer. Recently, Bifidobacterium adolescentis strains with high adhesion to intestinal epithelial cells were associated with induction of T-helper 17 (Th17) cells in humans and rodents. Here, two B. adolescentis strains with similar adhesive ability but different aggregation properties were investigated for specific immunoregulatory effects, including the underlying cellular pathway, on macrophage and T-regulatory (Treg)/Th17 axis activation in vitro and in the colon of dextran sodium sulfate (DSS)-colitis mice in vivo. In-vitro, the auto-aggregative B. adolescentis strain IF1-11 induced significantly higher IL-6 and lower IL-10 secretion from immune cells, and it induced abundant Th17 cells. The non-aggregating strain IF1-03 induced significantly higher IL-10, less IL-6 and a high proportion of Treg/Th17 cells compared to total T cells. In vivo, orally administered IF1-03 protected DSS-colitis mice via activation of dendritic cells or macrophages and skewing of Treg/Th17 cells, consistent with Treg cell induction in vitro. IF1-03 exopolysaccharides showed a functional recognition pattern similar to IF1-03 for IL-10 cytokine secretion and Treg cell-differentiation induction, both dependent on the toll-like receptor 2-ERK/p38 MAPK-signaling cascade for macrophage activation. We suggest that B. adolescentis exopolysaccharide-associated enterocyte adhesion/aggregation phenotypes determine strain-specific adaptive immune responses in the gut via the macrophage-regulated Treg/Th17 axis.


Assuntos
Aderência Bacteriana , Bifidobacterium adolescentis/metabolismo , Colite/prevenção & controle , Colo/microbiologia , Microbioma Gastrointestinal , Polissacarídeos Bacterianos/metabolismo , Probióticos/administração & dosagem , Linfócitos T Reguladores/microbiologia , Células Th17/microbiologia , Animais , Bifidobacterium adolescentis/imunologia , Colite/imunologia , Colite/metabolismo , Colite/microbiologia , Colo/imunologia , Colo/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Sulfato de Dextrana , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Interações Hospedeiro-Patógeno , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Polissacarídeos Bacterianos/imunologia , Células RAW 264.7 , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Receptor 2 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Neural Plast ; 2019: 2098083, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984253

RESUMO

Although referred pain or hypersensitivity has been repeatedly reported in irritable bowel syndrome (IBS) patients and experimental colitis rodents, little is known about the neural mechanisms. Spinal long-term potentiation (LTP) of nociceptive synaptic transmission plays a critical role in the development of somatic hyperalgesia in chronic pain conditions. Herein, we sought to determine whether spinal LTP contributes to the referral hyperalgesia in colitis rats and particularly whether electroacupuncture (EA) is effective to alleviate somatic hyperalgesia via suppressing spinal LTP. Rats in the colitis group (induced by colonic infusion of 2,4,6-trinitrobenzenesulfonic acid, TNBS), instead of the control and vehicle groups, displayed evident focal inflammatory destruction of the distal colon accompanied not only with the sensitized visceromotor response (VMR) to noxious colorectal distension (CRD) but also with referral hindpaw hyperalgesia indicated by reduced mechanical and thermal withdrawal latencies. EA at Zusanli (ST36) and Shangjuxu (ST37) attenuated the severity of colonic inflammation, as well as the visceral hypersensitivity and referral hindpaw hyperalgesia in colitis rats. Intriguingly, the threshold of C-fiber-evoked field potentials (CFEFP) was significantly reduced and the spinal LTP was exaggerated in the colitis group, both of which were restored by EA treatment. Taken together, visceral hypersensitivity and referral hindpaw hyperalgesia coexist in TNBS-induced colitis rats, which might be attributed to the enhanced LTP of nociceptive synaptic transmission in the spinal dorsal horn. EA at ST36 and ST37 could relieve visceral hypersensitivity and, in particular, attenuate referral hindpaw hyperalgesia by suppressing the enhanced spinal LTP.


Assuntos
Colite/fisiopatologia , Eletroacupuntura , Hiperalgesia/fisiopatologia , Potenciação de Longa Duração , Nociceptividade/fisiologia , Medula Espinal/fisiopatologia , Animais , Colite/induzido quimicamente , Colite/prevenção & controle , Modelos Animais de Doenças , Membro Posterior/fisiopatologia , Hiperalgesia/complicações , Masculino , Limiar da Dor , Ratos Sprague-Dawley , Ácido Trinitrobenzenossulfônico/administração & dosagem
20.
Cell Host Microbe ; 25(5): 681-694.e8, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31006637

RESUMO

The microbiota and the gastrointestinal mucus layer play a pivotal role in protection against non-typhoidal Salmonella enterica serovar Typhimurium (S. Tm) colitis. Here, we analyzed the course of Salmonella colitis in mice lacking a functional mucus layer in the gut. Unexpectedly, in contrast to mucus-proficient littermates, genetically deficient mice were protected against Salmonella-induced gut inflammation in the streptomycin colitis model. This correlated with microbiota alterations and enrichment of the bacterial phylum Deferribacteres. Using gnotobiotic mice associated with defined bacterial consortia, we causally linked Mucispirillum schaedleri, currently the sole known representative of Deferribacteres present in the mammalian microbiota, to host protection against S. Tm colitis. Inhibition by M. schaedleri involves interference with S. Tm invasion gene expression, partly by competing for anaerobic electron acceptors. In conclusion, this study establishes M. schaedleri, a core member of the murine gut microbiota, as a key antagonist of S. Tm virulence in the gut.


Assuntos
Antibiose , Bactérias Anaeróbias/crescimento & desenvolvimento , Colite/prevenção & controle , Infecções por Salmonella/prevenção & controle , Salmonella typhimurium/crescimento & desenvolvimento , Animais , Colite/induzido quimicamente , Modelos Animais de Doenças , Vida Livre de Germes , Camundongos
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