RESUMEN
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.
Asunto(s)
Apoptosis , Colitis Ulcerosa , Sulfato de Dextran , Estrés del Retículo Endoplásmico , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Apoptosis/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Colon/patología , Colon/efectos de los fármacos , Triterpenos/farmacología , Triterpenos/uso terapéutico , Ratones , Citocinas/metabolismo , Permeabilidad/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Inflammatory bowel disease (IBD) is a chronic inflammatory disease involving the digestive tract, characterized by abdominal pain, diarrhea, rectal bleeding, and so on, which can make patients physically weakened and live difficultly. Although IBD has been recognized for many years, the pathogenesis of IBD has not yet been established and damage to intestinal barrier is thought to be closely associated with IBD. Intestinal barrier is an innate barrier that maintains the homeostasis of the intestinal environment and impedes pathogenic bacteria and toxins, and the endoplasmic reticulum (ER) has recently been found to be involved in maintaining the integrity of intestinal barrier. Endoplasmic reticulum stress (ERS) is a status of endoplasmic reticulum damaged when unfolded or misfolded proteins accumulate in excess of the degradation systematic clearance limit of the misfolded proteins. The regulation of ERS on protein folding synthesis and maintenance of cellular homeostasis is an important factor in influencing the integrity of the intestinal barrier. This paper mainly discusses the relationship between ERS and the intestinal barrier, aiming to understand the regulatory role of ERS on the intestinal barrier and the mechanism and to improve new solutions and notions for the treatment or prevention of IBD.
Asunto(s)
Estrés del Retículo Endoplásmico , Enfermedades Inflamatorias del Intestino , Humanos , Estrés del Retículo Endoplásmico/fisiología , Intestinos , Enfermedades Inflamatorias del Intestino/metabolismo , Pliegue de Proteína , Retículo Endoplásmico/metabolismo , Mucosa Intestinal/metabolismo , Respuesta de Proteína DesplegadaRESUMEN
Baicalin is a plant-derived flavonoid from Scutellaria baicalensis Georgi with multiple bioactivities and has a protective effect against avian pathogenic Escherichia coli (APEC) infection. However, the underlying mechanism of baicalin against APEC infection is still unknown. Therefore, we aimed to explore whether the protective effects and mechanisms of baicalin on APEC-induced lung inflammation were related to the regulation of gut microbiota. The results showed that baicalin significantly reduced APEC colonization and pro-inflammatory cytokines production, and additionally recovered air-blood barrier integrity in the lungs after APEC challenge. However, depletion of gut microbiota significantly weakened the protective effects of baicalin against APEC infection as mentioned above. Furthermore, baicalin markedly restored the dysbiosis of gut microbiota induced by APEC as well as increased the abundance of short chain fatty acid (SCFA)-producing bacteria and the production of SCFAs including acetic acid, propionic acid and butyric acid, especially acetic acid. In addition, the concentrations of acetic acid and its receptor free fatty acid receptor 2 (FFAR2) were significantly upregulated in the lung tissues after baicalin treatment. In conclusion, gut microbiota played a key role in the pharmacological action of baicalin against APEC-induced lung inflammation. Baicalin remodeled the dysbiosis of gut microbiota caused by APEC and increased the production of SCFAs, especially acetic acid in the gut, and then the increased acetate may circulate to the lungs to activate FFAR2 to defend APEC infection. Together, our study suggested that baicalin inhibited APEC infection through remodeling the gut microbiota dysbiosis and increasing the SCFA production. Furthermore, baicalin may serve as an alternative antibiotic and a novel therapeutic drug to prevent or treat APEC infection.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Infecciones por Escherichia coli/complicaciones , Ácidos Grasos Volátiles/metabolismo , Flavonoides/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Lesión Pulmonar/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/metabolismo , Pollos , Modelos Animales de Enfermedad , Infecciones por Escherichia coli/metabolismo , Flavonoides/metabolismo , Lesión Pulmonar/etiología , Lesión Pulmonar/metabolismo , MasculinoRESUMEN
Chicken colibacillosis is caused by avian pathogenic Escherichia coli (APEC), and results in huge economic losses to the poultry industry. With the investigation of the gut-lung axis, more studies have demonstrated the important role of gut microbiota in lung inflammation. The precise role of the gut microbiota in chickens-associated colibacillosis, however, is unknown. Thus, this study assessed the function of the gut microbiota in the chicken defense against APEC infection. Chicken gut microbiota was depleted by drinking water with a mixture of antibiotics (Abx), and subsequently, a model of colibacillosis was established by the intranasal perfusion of APEC. The results showed that gut microbiota protects the chicken challenge by APEC from aggravated lung histopathologic injury, up-regulated pro-inflammatory cytokine production, and increased bacterial load in lung tissues compared with controls. In addition, the air-blood barrier permeability was significantly increased in gut microbiota-depleted chickens compared to the control chickens after challenge with APEC. Furthermore, feeding acetate significantly inhibited the lung inflammatory response and the reduced air-blood permeability induced by APEC infection. The expression of free fatty acid receptor 2 (FFAR2), a receptor for acetate, was also increased in the lung after treatment with acetate. In conclusion, depletion of the gut microbiota resulted in increased susceptibility of chickens to APEC challenge, and gut microbiota derived acetate acted as a protective mediator during the APEC challenge. Novel therapeutic targets that focus on the gut microbiota may be effective in controlling colibacillosis in poultry.
Asunto(s)
Acetatos/metabolismo , Antibiosis/fisiología , Infecciones por Escherichia coli/veterinaria , Microbioma Gastrointestinal/fisiología , Enfermedades de las Aves de Corral/microbiología , Animales , Pollos , Escherichia coli/fisiología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/prevención & controlRESUMEN
OBJECTIVE: To investigate the protective effects and mechanisms of sesamin (SES) on dextran sulfate sodium (DSS)-induced experimental colitis in mice. METHODS: SES (50, 100, and 200 mg kg-1) were orally administered to C57BL/6 male mice after DSS instillation. The anti-inflammatory effect of SES on colonic damage was assessed by clinical, macroscopic, microscopic, and inflammatory signaling pathways. RESULTS AND CONCLUSIONS: It could be found that bodyweight and colon length of mice treated with DSS was significantly decreased while that were increased by SES treatment. SES treatment reduced the DAI values and improved the histopathology of the colon in the DSS-treated mice. SES also reduced TNF-α, IL-1ß and IL-6 production caused by DSS. We also measured the expression of the phosphorylation of p65, IκB, p38, ERK and JNK protein and found that SES can alleviate colon damage via the NF-κB and MAPK signaling pathways. The findings of this study suggested that SES had anti-inflammatory effects on intestinal inflammation and can be used as a new therapeutic candidate for inflammatory bowel disease.
Asunto(s)
Colitis , Sulfato de Dextran/efectos adversos , Dioxoles/farmacología , Lignanos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/metabolismo , Animales , Antiinflamatorios/farmacología , Colitis/inducido químicamente , Colitis/metabolismo , Colon/efectos de los fármacos , Colon/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacologíaRESUMEN
Madecassoside (MA), a crucial ingredient of Centella asiatica, has been reported to exhibit a variety of bioactivities, including antipulmonary fibrosis, and antiinflammatory effects. Here we aimed to elucidate the protective effects and underlying mechanisms of MA on LPS-induced acute lung injury (ALI). The mice were treated with MA for one week and then received intratracheal of LPS to establish the ALI model. Then we evaluated the pathological changes by haematoxylin and eosin staining and measured the levels of proinflammatory cytokines and myeloperoxidase (MPO) by ELISA, the transcriptional level of tight junction proteins by qRT-PCR, as well as the expression of Toll-like receptor4/Nuclear factor kappa-B (TLR4/NF-κB) pathway by Western blot. The results showed that MA significantly inhibited LPS-induced pathological damages, lung edema, MPO, and proinflammatory cytokines production. Furthermore, MA obviously repaired alveolar epithelium integrity showing by reduced secretion of total proteins in the BALF and enhanced mRNA expression of tight junction as Occludin and zonula occludens-1 (ZO-1) comparing to LPS. Further research showed that LPS stimulation activated the TLR4/NF-κB signaling pathway and the activation was inhibited by MA. In conclusion, these data indicated that MA had protective effects against LPS-induced ALI. The therapeutic mechanisms may be associated with reducing the alveolar epithelium permeability and inflammatory response via repressing the activation of TLR4/NF-κB pathway.
RESUMEN
Avian pathogenic Escherichia coli (APEC) is a kind of highly pathogenic parenteral bacteria, which adheres to chicken type II pneumocytes through pili, causing inflammatory damage of chicken type II pneumocytes. Without affecting the growth of bacteria, anti-adhesion to achieve anti-inflammatory effect is considered to be a new method for the treatment of multi-drug-resistant bacterial infections. In this study, the anti-APEC activity of schizandrin was studied in vitro. By establishing the model of chicken type II pneumocytes infected with APEC-O78, the adhesion number, the expression of virulence genes, the release of lactate dehydrogenase (LDH), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were detected. The results showed that schizandrin reduced the release of LDH and the adherence of APEC on chicken type II pneumocytes. Moreover, schizandrin markedly decreased the levels of IL-1ß, IL-8, IL-6, and TNF-α, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings revealed that schizandrin could reduce the inflammatory injury of chicken type II pneumocytes by reducing the adhesion of APEC-O78 to chicken type II pneumocytes. The results indicate that schizandrin can be a potential agent to treat inflammation caused by avian colibacillosis.
Asunto(s)
Células Epiteliales Alveolares/fisiología , Antiinflamatorios/uso terapéutico , Ciclooctanos/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli/fisiología , Inflamación/tratamiento farmacológico , Lignanos/uso terapéutico , Compuestos Policíclicos/uso terapéutico , Enfermedades de las Aves de Corral/tratamiento farmacológico , Animales , Adhesión Bacteriana , Células Cultivadas , Pollos , Citocinas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Mediadores de Inflamación/metabolismo , L-Lactato Deshidrogenasa/metabolismo , FN-kappa B/metabolismo , Transducción de SeñalRESUMEN
Acute liver injury can be caused by chemicals and can lead to liver failure. We investigated the protective effect of helicid (HEL) on acute liver injury caused by CCl4 in mice. We found that ALT and AST levels as well as hepatic pathological damage in mice treated with CCl4 was increased significantly, while the effects were decreased by HEL treatment. HEL treatment increased the activity of T-SOD, GSH and CAT and reduced the level of MDA in CCl4 treated mice. HEL improved the histopathology of liver caused by CCl4. HEL also reduced TNF-α, IL-1ß and IL- 6 activity caused by CCl4. We investigated the phosphorylation of p65 and IκB protein and found that HEL can alleviate liver damage via the NF-κB signaling pathway. Our findings indicate that HEL protects against acute liver injury induced by CCl4. The protective effect of HEL appears to be due to its antioxidative and anti-inflammatory properties through the NF-κB signaling pathway.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Benzaldehídos/uso terapéutico , Intoxicación por Tetracloruro de Carbono/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Alanina Transaminasa/metabolismo , Animales , Antiinflamatorios/química , Antioxidantes/química , Aspartato Aminotransferasas/metabolismo , Benzaldehídos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/genética , FN-kappa B/metabolismoRESUMEN
Avian pathogenic Escherichia coli (APEC) can cause serious pathological changes and inflammation in chickens. Schizandrin has anti-inflammatory activity and can prevent damage to various tissues and organs. The purpose of this study was to investigate the protective effect of schizandrin on APEC-induced lung lesions in chickens and explore the potential mechanism of schizandrin protection. The schizandrin (50, 100, and 200 mg/kg) was intragastrically administered for 3 days. APEC was administered using intraperitoneal (i.p.) injection to induce lung lesions. Then, chickens were sacrificed by CO2 inhalation 24 h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Our findings showed that schizandrin markedly inhibited pathological changes, pulmonary edema, MPO activity and MDA content. Moreover, schizandrin markedly reduced the levels of TNF-α, IL-1ß, IL-6 and IL-8 in lung tissue. Importantly, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings reveal that schizandrin displays anti-oxidant and anti-inflammatory activity against APEC-induced lung lesions in chickens, paving the way for rational use of schizandrin as a protective agent against lung-related inflammatory disease.
RESUMEN
Avian pathogenic Escherichia coli (APEC) causes great economic loss to the poultry industry worldwide. Chicken type II pneumocytes (CP II cells) secrete surfactants and modulate lung immunity to decrease the infection of the invading pathogen. Nevertheless, the pathogenesis of CP II cells to APEC infection remains poorly understood. Therefore, we conducted global gene expression profiling of CP II cells after APEC-O78 infection to explore the host-pathogen interaction. The differentially expressed genes of CP II cells to APEC infection were characterized by RNA-seq with EB-seq algorithm. In consequence, the mRNA of 18996 genes was identified, and CP II cells responded to APEC infection with marked changes in the expression of 1390 genes. Among them, there are 803 down-regulated mRNAs and 587 up-regulated mRNAs. The KEGG prediction and Gene Ontology terms analysis revealed that the major enriched pathways were related to NF-κB signaling pathway, apoptosis pathway, tight junction, and cytokine-cytokine receptor interaction and other pathways. We adopted qRT-PCR to verify the validity of the selected gene expression. The fold induction of qPCR was similar to the RNA-seq results. These results provide a better understanding of the pathogenesis of APEC, especially apoptosis pathway involved in APEC infection.
Asunto(s)
Células Epiteliales Alveolares/metabolismo , Proteínas Aviares/biosíntesis , Pollos/metabolismo , Infecciones por Escherichia coli/metabolismo , Escherichia coli , Regulación de la Expresión Génica , Enfermedades de las Aves de Corral/metabolismo , Análisis de Secuencia de ARN , Células Epiteliales Alveolares/microbiología , Animales , Pollos/microbiología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/patología , Infecciones por Escherichia coli/veterinaria , Enfermedades de las Aves de Corral/microbiología , ARN Mensajero/biosíntesis , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Canine distemper virus (CDV) can cause a highly contagious disease to canid. However, how CDV affects peripheral blood lymphocyte (PBL) remains unclear. METHODS: In this study, CDV infected PBL was cultured to investigate the effect of CDV on the differentiation of lymphocytes and the mRNA expression of inflammatory cytokines in PBL. RESULTS: The results showed that CDV changed the phenotype of lymphocytes and increased the percentage of CD4+CD8+ T cells. To explore the effect of immune response of lymphocytes to CDV, the mRNA expression of pro- and anti-inflammatory cytokines was examined. Interleukin (IL-6, IL-12B), and tumor necrosis factor (TNF)-α mRNA expression was significantly increased at 12-48â¯h after CDV infection. IL-10 mRNA expression was dramatically enhanced at 12-36â¯h after CDV infection. However, IL-4 and transforming growth factor (TGF-ß) were not response to CDV infection. These results indicated that PBL differentiated intoCD4+CD8+ T cells and improved the inflammatory response to CDV infection. CONCLUSIONS: After CDV infection, PBL differentiated into CD4+CD8+ T cells and initiated inflammatory response.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Diferenciación Celular , Citocinas/metabolismo , Virus del Moquillo Canino/patogenicidad , Moquillo/inmunología , Linfocitos/metabolismo , ARN Mensajero/metabolismo , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Moquillo/virología , Perros , Femenino , Interleucina-10/metabolismo , Linfocitos/inmunología , Fenotipo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Bacterial pneumonia is a leading cause of death in the animal husbandry. Acute lung injury (ALI), most often seen as a part of systemic inflammatory process, characterized by progressive hypoxemia, edema, and neutrophil accumulation in the lung. Baicalin has been reported to inhibit inflammatory response, but its role in ALI remains unknown. The purpose of our study was to determine the protective effect and possible mechanism of baicalin against avian pathogenic Escherichia coli (APEC)-induced ALI in chicken. Chickens were conditioned with baicalin 1â¯week before intratracheally instilled with APEC. Then, chickens were sacrificed by CO2 inhalation 12â¯h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, levels of pro-inflammatory cytokines and activation of NF-κB signaling pathway. The results showed that pre-treatment of chickens with baicalin significantly alleviated the death rate, histopathological changes in lung tissues. The W/D ratio, MPO activity and production of cytokines, such as IL-1ß, TNF-α, IL-6 of lung tissues were also decreased following treatment with baicalin. Furthermore, the mechanism responsible for these effects was attributed to the inhibitory effect of baicalin on nuclear factor-κB (NF-κB) signaling activation. These data thus support the application of baicalin as a potential medicine for the treatment of E. coli-induced ALI by regulating NF-κB signaling pathway.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Infecciones por Escherichia coli/tratamiento farmacológico , Flavonoides/uso terapéutico , FN-kappa B/inmunología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/veterinaria , Animales , Pollos , Citocinas/inmunología , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/patología , Infecciones por Escherichia coli/veterinaria , Flavonoides/farmacología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/patología , Transducción de Señal/efectos de los fármacosRESUMEN
Avian pathogenic Escherichia coli (APEC), collectively known as causative agent of extraintestinal infections, is an important cause of morbidity and mortality in poultry. Currently, quorum sensing (QS), biofilm formation and virulence factors are considered as novel prospective targets for antimicrobial therapy to control APEC invasion. In addition, inflammatory responses are also served as the major pathological features of APEC invasion. This study was aimed to explore the effect of baicalin on APEC and APEC-induced inflammatory responses. After treatment with baicalin, we mainly examined the AI-2 secretion, biofilm formation, expression of virulence genes of APEC, and the levels of inflammatory cytokines, as well as the expression of NF-κB pathway. Our results showed that baicalin significantly inhibited the QS via decreasing the AI-2 secretion, biofilm formation, and the expression of virulence genes of APEC such as LsrB, LsrK, LuxS, pfs, H-NS, fimA, fimB, fyuA, csgA, csgB, and rpoS. Moreover, baicalin significantly attenuated the release of lactate dehydrogenase (LDH), and the adhesion of APEC to chicken type II pneumocytes to reduce cell damage. Furthermore, baicalin also inhibited the expression of pro-inflammatory cytokines and NF-κB activation. Thus, our data revealed that baicalin could interfere with the quorum sensing, biofilm formation and virulence genes expression to relieve the APEC pathogenicity. Additionally, baicalin decreased the inflammatory responses of chicken type II pneumocytes induced by APEC. Taken together, these data provide a novel potential pharmaco-therapeutic approach to chicken colibacillosis.
Asunto(s)
Infecciones por Escherichia coli/prevención & control , Escherichia coli/efectos de los fármacos , Flavonoides/farmacología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Percepción de Quorum/efectos de los fármacos , Animales , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Pollos , Proteínas de Unión al ADN/genética , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Integrasas/genética , Aves de Corral/genética , Enfermedades de las Aves de Corral/microbiología , Percepción de Quorum/genéticaRESUMEN
Acute lung injury (ALI) is a common and complex inflammatory lung syndrome with higher morbidity and mortality rate. Piceatannol (PIC) has anti-inflammation and anti-oxidant properties. The study was designed to explore the effect and the action mechanisms of PIC on lipopolysaccharide (LPS)-induced ALI. Twenty-four hours after LPS challenge, mice from different treatment groups were euthanized, and the bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. Then the degree of pulmonary edema, lung pathological changes, myeloperoxidase (MPO) activity, and the production of pro-inflammatory cytokines were detected. Additionally, the messenger RNA (mRNA) expressions associated with cell adhesion molecules and tight junction were analyzed through quantitative real-time (qRT)-PCR, and the TLR4/NF-κB activation was examined by western blot. The results showed that PIC significantly inhibited LPS-induced lung edema, histopathological damage, MPO activity, cell infiltration, and pro-inflammatory cytokines production. Moreover, PIC notably suppressed mRNA expressions associated with inflammation and cell adhesion molecules. Furthermore, PIC also alleviated LPS-induced damage of air-blood barrier through reducing the levels of total proteins in BALF and recovering the expression of occludin and ZO-1 in the lung tissues. We also found that PIC remarkably restrained the LPS-induced TLR4/NF-κB pathway activation in lung tissues. In conclusion, PIC may be potential to treat LPS-induced acute lung injury (ALI) via regulating air-blood barrier and TLR4/NF-κB signaling pathway activation.
RESUMEN
The study aimed to investigate whether rutin affects the quorum sensing (QS) of avian pathogenic Escherichia coli (APEC). In this study, APEC-O78 was selected as the test strain. We mainly examined the effects of rutin on the AI-2 secretion by bioluminescence assay, biofilm formation through a crystal violet staining method, and expression of virulence genes of APEC by qRT-PCR. We found that rutin can significantly interfering with QS through reducing the secretion of AI-2, inhibited the biofilm formation, and reduced the expression of virulence genes of APEC. Moreover, rutin markedly decreased adhesion and damage of APEC to chicken type II pneumocytes. These results suggested rutin reduces cell damage of APEC-infected chicken type II pneumocytes through interfering with QS via decreasing AI-2 production, biofilm formation, and the expression of virulence genes. This paper may provide a new evidence for colibacillosis prevention in chicken.
Asunto(s)
Biopelículas/efectos de los fármacos , Infecciones por Escherichia coli/veterinaria , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Rutina/antagonistas & inhibidores , Factores de Virulencia/genética , Adhesinas Bacterianas/efectos de los fármacos , Células Epiteliales Alveolares/microbiología , Animales , Biopelículas/crecimiento & desarrollo , Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/genética , Supervivencia Celular/efectos de los fármacos , Pollos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica/genética , L-Lactato Deshidrogenasa/análisis , Pruebas de Sensibilidad Microbiana , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/microbiología , Rutina/química , Virulencia/efectos de los fármacos , Virulencia/genéticaRESUMEN
Canine distemper (CD) is a highly contagious disease caused by the canine distemper virus (CDV), and mortality can be as high as 100%. However, there is no specific treatment for CD. In this study, the antiviral activity of the caffeic acid against CDV was evaluated in vitro. The results showed that the IC50 of the caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3 µg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a reduced (23.3-57.0% and 37.2-38.1%) viral inhibitory effect in vero cells. Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity against CDV than the caffeic acid or RBV individually. In addition, the caffeic acid reduced the total viral RNA synthesis by 59-86% at 24-72 h. Therefore, our data provided the experimental evidence that the caffeic acid effectively inhibited CDV infection in vero cells, which may potentially be used to treat clinical disease associated with CDV infection.
Asunto(s)
Antivirales/farmacología , Ácidos Cafeicos/farmacología , Virus del Moquillo Canino/efectos de los fármacos , Moquillo/tratamiento farmacológico , Animales , Antivirales/administración & dosificación , Antivirales/química , Antivirales/uso terapéutico , Ácidos Cafeicos/administración & dosificación , Ácidos Cafeicos/química , Ácidos Cafeicos/uso terapéutico , Chlorocebus aethiops , Moquillo/virología , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Concentración 50 Inhibidora , ARN Viral/metabolismo , Ribavirina/farmacología , Ribavirina/uso terapéutico , Factores de Tiempo , Células Vero/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Oroxylin A, a natural flavonoid isolated from Scutellaria baicalensis, has been reported to have anti-inflammatory and antioxidant effects. However, suppression of oxidative stress and neuroapoptosis by oroxylin A is largely uninvestigated. To investigate the protective effects of oroxylin A, PC12 cells were exposed to oroxylin A and hydrogen peroxide solutions and measured. Oroxylin A signiï¬cantly reduced the levels of intracellular calcium and reactive oxygen species and increased the levels of CAT and Mn/SOD. Oroxylin A also inhibited the activation of caspase-3. These results suggest that treatment of PC12 cells with oroxylin A inhibits H2O2-induced oxidative stress.
Asunto(s)
Flavonoides/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Peróxido de Hidrógeno/farmacología , Células PC12 , Extractos Vegetales , Ratas , Especies Reactivas de Oxígeno/metabolismo , Scutellaria baicalensis , Superóxido Dismutasa/metabolismoRESUMEN
Avian pathogenic Escherichia coli (APEC) infections are responsible for great losses in the poultry industry. Quorum sensing (QS) acts as a global regulatory system that controls genes involved in bacterial pathogenesis, metabolism and protein biosynthesis. However, whether QS of APEC is related to cell damage has not been elucidated. In the present study, we explored the correlation between the damage of chicken type II pneumocytes induced by APEC and the autoinducer-2 (AI-2) activity of APEC. The results showed that when chicken type II pneumocytes were co-cultured with 108 CFU/ml of APEC-O78 for 6 h, the release of LDH reached the highest level (192.5 ± 13.4 U/L) (P < 0.01), and the percentages of dead cells followed the same trend in trypan blue exclusion assay. In addition, the AI-2 activity of cell-free culture fluid (CF) reached the maximum value after 6 h co-culture with 108 CFU/ml of APEC-O78. At the same time, the mRNA expressions of eight virulence genes (papC, fimA, fimC, hlyE, ompA, luxS, pfs, and qseA) of 108 CFU/ml APEC-O78 were significantly increased compared with those of 107 CFU/ml, and the mRNA expressions of four virulence genes (hlyE, tsh, iss, and luxS) of 108 CFU/ml APEC-O78 were higher than those of 109 CFU/ml (p < 0.05) after incubation for 6 h. These results suggested that AI-2-mediated QS is involved in the cell damage induced by APEC-O78, indicating AI-2 may be one new potential target for preventing chicken colibacillosis.
Asunto(s)
Células Epiteliales Alveolares/microbiología , Células Epiteliales Alveolares/fisiología , Escherichia coli/patogenicidad , Homoserina/análogos & derivados , Lactonas/metabolismo , Factores de Virulencia/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Pollos , Técnicas de Cocultivo , Escherichia coli/fisiología , Homoserina/metabolismo , L-Lactato Deshidrogenasa/análisis , Percepción de Quorum , Coloración y Etiquetado , Azul de Tripano/análisisRESUMEN
Cinobufagin (CBG), one active ingredient isolated from Venenum Bufonis, has been demonstrated to have immunoregulatory effect. The aim of this study was to investigate whether CBG can enhance the protective efficacy of formalin-inactivated Salmonella typhimurium (FIST) in mice. ICR mice were immunized with FIST (106 CFU/mouse) alone or mixed with CBG (10, 20, and 40 µg) or alum (200 µg) on day 1 and day 15. Two weeks after the second immunization, serum and spleen were sampled for measuring FIST-specific antibody levels, cytokine levels, and splenocyte proliferation. The results showed that CBG enhanced FIST-specific IgG and IgG2a, the levels of interferon-gamma (IFNγ) and nitric oxide (NO), and the splenocyte proliferation response induced by concanavalin A, lipopolysaccharide, and FIST. In vivo protection studies showed that CBG significantly decreased the bacterial burdens in the spleen and prolonged the survival time of FIST-immunized mice challenged with live Salmonella typhimurium. In vivo IFNγ neutralization led to a significant reduction in FIST-specific IgG2a and IFNγ levels, and in the protective efficacy in CBG/FIST-immunized mice. In conclusion, CBG enhances the protective efficacy of formalin-inactivated Salmonella typhimurium vaccine by promoting the Th1 immune response.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Bufanólidos/administración & dosificación , Vacunas contra la Salmonella/inmunología , Salmonella typhimurium/inmunología , Células TH1/inmunología , Compuestos de Alumbre/administración & dosificación , Animales , Anticuerpos Antibacterianos/sangre , Proliferación Celular , Citocinas/análisis , Modelos Animales de Enfermedad , Fijadores , Formaldehído , Esquemas de Inmunización , Inmunoglobulina G/sangre , Leucocitos Mononucleares/inmunología , Ratones Endogámicos ICR , Salmonelosis Animal , Vacunas contra la Salmonella/administración & dosificación , Suero/inmunología , Bazo/inmunología , Bazo/microbiología , Análisis de Supervivencia , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Avian pathogenic Escherichia coli (APEC) induces septicemia in chickens by invading type II pneumocytes after breaching the blood-air barrier. Type II pneumocytes play an important role in maintaining the function of the blood-air barrier. Astragaloside IV has been shown in previous studies to have an anti-inflammatory effect. To explore whether astragaloside IV can inhibit APEC-induced injury in chicken type II pneumocytes, cells were infected with APEC-O78. The results showed that astragaloside IV significantly reduced cell damage in chicken type II pneumocytes induced by APEC-O78 by downregulating the production of TNF-α and IL-1ß, upregulating the secretion of IL-4 and IL-10, suppressing the mRNA levels of TLR-4, TLR-5, ERK, and p38 of chicken type II pneumocytes as well as inhibiting bacterial adhesion and F-actin cytoskeleton polymerization. These results suggest that astragaloside IV may be useful in novel pharmaco-therapeutic approaches to the treatment of chicken colibacillosis.