RESUMO
In Crohn's disease (CD), gut dysbiosis is marked by the prevalence of pathogenic bacterial species. Although several microbes have been reported as risk factors or causative agents of CD, it is not yet clear which is the real trigger of the disease. Thirty years ago, a new pathovar of Escherichia coli strain was isolated in the ileal mucosa of CD patients. This strain, called adherent invasive E. coli (AIEC), for its ability to invade the intestinal mucosa, could represent the causative agent of the disease. Several authors studied the mechanisms by which the AIEC penetrate and replicate within macrophages, and release inflammatory cytokines sustaining inflammation. In this review we will discuss about the role of AIEC in the pathogenesis of CD, the virulence factors mediating adhesion and invasion of AIEC in mucosal tissue, the environmental conditions improving AIEC survival and replication within macrophages. Finally, we will also give an overview of the new strategies developed to limit AIEC overgrowth.
Assuntos
Doença de Crohn , Infecções por Escherichia coli , Humanos , Doença de Crohn/epidemiologia , Doença de Crohn/microbiologia , Doença de Crohn/patologia , Escherichia coli , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Aderência Bacteriana , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologiaRESUMO
SCOPE: Polyphenols exhibit their antioxidant activity downstream the activation of the nuclear factor erythroid 2-related factor 2 pathway (Nrf2), but the connection between lipid metabolism and the Nrf2 pathway is still unknown. Flavonoid-rich concentrated extract from Prunus mahaleb (mahaleb concentrated fruit extract; MCFE) may act on oxido-reductive homeostasis and hepatic lipid metabolism via Nrf2. METHODS & RESULTS: MCFE ability to enhance the activity of Nrf2-mediated antioxidant/detoxifying enzymes is investigated in liver and colon of BALB/c mice. After a 4-week supplementation, macroscopic, histological, and biochemical signs of colitis are examined in mouse colon pulsed with 5% (w/v) dextran sodium sulfate (DSS). Untreated or DSS-supplemented mice are used as negative or positive control. MCFE effect on liver lipid metabolism and its possible link with the Nrf2 pathway is investigated. MCFE intake increases antioxidant defenses in mice colon and its pretreatment blunts pathological signs of colitis, as compared to positive control. In the liver, the increase in antioxidant defenses is associated with enhanced oxidative metabolism and with higher levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and of hemeoxygenase-1 (HO-1), in comparison with negative controls. CONCLUSION: Cytoprotective and hypolipidemic effect produced by MCFE intake results, at least in part, by the activation of the Nrf2 pathway.
Assuntos
Colite/prevenção & controle , Mitocôndrias/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/fisiologia , Extratos Vegetais/farmacologia , Prunus , Animais , Sulfato de Dextrana , Feminino , Frutas , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/fisiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Laser capture microdissection (LCM) is a powerful tool for selection and isolation of single cells or compartments from complex primary tissues to perform molecular analyses. Celiac disease is a genetic autoimmune disorder where the ingestion of gluten leads to damage in the small intestine. Increased intraepithelial lymphocytes and the presence of the lamina propria inflammatory infiltrate of the duodenal mucosa is a common part of the disease. These cells promote inflammatory processes through the release of cytokines. Here, we describe the use of LCM and real-time quantitative PCR (RT-qPCR) to analyze cytokine profile information in distinct duodenal mucosa tissue compartments of celiac patients.
Assuntos
Doença Celíaca/metabolismo , Citocinas/genética , Duodeno/metabolismo , Imunidade nas Mucosas , Mucosa Intestinal/metabolismo , Microdissecção e Captura a Laser/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Doença Celíaca/imunologia , Citocinas/metabolismo , HumanosRESUMO
Different approaches have been used to study the pattern of cytokines in celiac disease (CD). Laser capture microdissection (LCM) is a powerful tool for the isolation of specific tissue compartments. We aimed to investigate the mucosal immune response that takes place in different intestinal compartments of CD patients, dissected by LCM, analyzing cytokine expression profile. Frozen section of jejunum was obtained from 15 untreated CD and 15 control. Surface epithelium and lamina propria compartment were isolated by LCM. RNA from each LCM sample was extracted and, after a retrotranscription step, messenger RNA levels for MxA, IL-15, TNF-α, IFN-γ, IL-17α, IL-21, IL-10, and TGF-ß were determined by quantitative reverse transcriptase-PCR. Increased gene expression levels of MxA, IL-15, TNF-α, IL-10, and TGF-ß was observed in the surface epithelium of untreated CD with respect to control. Furthermore, all the cytokines investigated were upregulated in the lamina propria of untreated CD as compared to control. Within the untreated CD group the expression of IL-15 was higher, in the surface epithelium than in the lamina propria, whereas the expression levels of IL-17 and IL-21 were higher in the lamina propria than in the surface epithelium. Finally, high levels of IL-10 and TGF-ß were detected in both compartments of untreated CD biopsies. In CD, surface epithelium and lamina propria compartments, play a prominent role in determining innate and adaptive immunity, respectively. Conversely, surface epithelium and lamina propria produce high levels of anti-inflammatory cytokines, suggesting that both compartments are involved in the immunoregulatory response.