RESUMEN
Dietary intervention in type 2 diabetes mellitus (T2DM) is a hotspot in international research because of potential threats to human health. Phellinus baumii, a wild fungus traditionally used as a food and medicine source, is now cultivated in certain East Asian countries, and is rich in polyphenols, which are effective anti-inflammatory ingredients useful in treatment of T2DM, with fewer side effects than drugs. To examine the hypoglycaemic effects of Phellinus baumii phenolics (PPE), the metabolite profiles of T2DM mice induced by streptozotocin after PPE intervention were systematically analyzed. Here, 10 normal mice were given normal saline as control group, and 50 model mice were randomly assigned to five groups and daily intragastric administrated with saline, metformin (100 mg/kg), and PPE (50, 100, 150 mg/kg of body weight), for 60 days. The pro-inflammatory factor contents of lipopolysaccharide stimulation of RAW 264.7 cells were decreased in a dose-dependent manner after PPE treatment, we propose that PPE could exert anti-inflammatory properties. PPE could also effectively reduce blood glucose levels, increased insulin sensitivity, and improved other glucolipid metabolism. Q-PCR results suggested that the hypoglycemic effects of PPE might be through activating IRS1/PI3K/AKT pathway in diabetic mice. These results suggest that PPE has strong potential as dietary components in the prevention or management of T2DM.
Asunto(s)
Phellinus/química , Fenoles/uso terapéutico , Animales , Basidiomycota/efectos de los fármacos , Basidiomycota/patogenicidad , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Lipopolisacáridos/fisiología , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Reacción en Cadena de la Polimerasa , Células RAW 264.7RESUMEN
Spinal cord injury (SCI) is a functional impairment of the spinal cord caused by external forces, accompanied by limb movement disorders and permanent paralysis, which seriously lowers the life quality of SCI patients. Secondary injury caused by inflammation attenuated the therapeutic effects of SCI. Therefore, the exploration of biomarkers associated with the inflammatory response following SCI might provide novel therapy strategy against SCI.SCI rat model was established as previously reported and evaluated by BBB score. The expression of microRNA-24-3p (miR-24-3p) and MAPK-activated protein kinase 2 (MK2) in spinal cord tissues of SCI rats and HAPI cells was analyzed by qRT-PCR. Protein expression of MK2, ionized calcium-binding adapter molecule-1 (Iba-1), tumor necrosis factor-alpha (TNF-α), and interleukin-1ß (IL-1ß) was assessed by western blot assay. The release of inflammatory cytokines TNF-α and IL-1ß was measured by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-24-3p and MK2 was examined by the luciferase reporter system. Basso-Beattie-Bresnahan (BBB) score dramatically reduced in rats following SCI compared with sham rats. Moreover, the expression of miR-24-3p was down-regulated, while MK2 was up-regulated in the spinal cord tissues of SCI rats and LPS-induced microglia cells compared with the corresponding control group. Luciferase reporter system confirmed the interaction between miR-24-3p and MK2. In addition, miR-24-3p upregulation or MK2 knockdown attenuated LPS induced activation of microglial cells and expression of inflammatory cytokine TNF-α and IL-1ß. Besides, we discovered that miR-24-3p regulated inflammation of highly aggressively proliferating immortalized (HAPI) cells by targeting MK2.In our study, we clarified that miR-24-3p repressed inflammation of microglia cells following SCI by regulating MK2, thereby providing promising biomarkers for SCI therapy.
Asunto(s)
Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , MicroARNs/metabolismo , Microglía/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo/fisiología , Humanos , Inflamación/etiología , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Lipopolisacáridos/fisiología , Microglía/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/deficiencia , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/complicaciones , Regulación hacia Arriba/fisiologíaRESUMEN
BACKGROUND: Aortic valve interstitial cells have been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimuli, aortic valve interstitial cells undergo an osteogenic phenotypic change. The purpose of this study was to determine whether the anti-inflammatory effects of statins prevent osteogenic activity in cultured aortic valve interstitial cells. METHODS: Human aortic valve interstitial cells were isolated from hearts explanted for cardiac transplantation. To test whether simvastatin down-regulates TLR4-induced osteogenic response, aortic valve interstitial cells were treated with simvastatin with and without TLR4 agonist lipopolysaccharide (LPS), and osteogenic markers were measured. Simvastatin's influence on in vitro calcium deposition was assessed by alizarin red staining. Knockdown of postreceptor signaling proteins (MyD88 and TRIF) was performed to determine which of 2 TLR4-associated pathways mediates the osteogenic response. Expression levels of TLR4-induced nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and TLR4 expression were assessed after treatment with simvastatin. Statistical testing was done by analysis of variance (P < .05). RESULTS: Simvastatin decreased LPS-induced ALP and Runx2 expression and inhibited in vitro calcium deposition in aortic valve interstitial cells. Knockdown of MyD88 and TRIF attenuated the osteogenic response. Simvastatin attenuated TLR4-dependent NF-κB signaling and down-regulated TLR4 levels. CONCLUSIONS: Simvastatin prevented TLR4-induced osteogenic phenotypic changes in isolated aortic valve interstitial cells via down-regulation of TLR4 and inhibition of NF-κB signaling. These data offer mechanistic insight into a possible therapeutic role for simvastatin in the prevention of aortic stenosis.
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Válvula Aórtica/efectos de los fármacos , Válvula Aórtica/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Osteogénesis/efectos de los fármacos , Simvastatina/farmacología , Proteínas Adaptadoras del Transporte Vesicular/fisiología , Fosfatasa Alcalina/metabolismo , Válvula Aórtica/metabolismo , Técnicas de Cultivo de Célula , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Humanos , Lipopolisacáridos/fisiología , Factor 88 de Diferenciación Mieloide/fisiología , FN-kappa B/metabolismo , Transducción de Señal , Receptor Toll-Like 4/fisiologíaRESUMEN
The toxic effects of aflatoxin B1 (AFB1 ) on the physiological functions of swine alveolar macrophages (SAM) were investigated. Freshly isolated SAM were incubated with various AFB1 concentrations (1.6 × 10-1 - 1.6 × 105 nmol/L) and time periods, and their phagocytic ability, synthesis of DNA, RNA and protein, and cell activation by lipopolysaccharide (LPS), were analysed. Results demonstrated that a significant (p < .05) reduction (60%) in Staphylococcus aureus uptaken by SAM appeared 3 hr after AFB1 (>16 nmol/L) treatment. The synthesis of DNA, RNA and protein were markedly reduced, among which DNA and protein synthesis were affected more noticeably. The activation of SAM by LPS was significantly (p < .05) suppressed when the concentration of AFB1 reached 1.6 × 103 nmol/L. In general, most of the analysed effects were more prominent as AFB1 concentration or incubation period increased. Taken together, AFB 1 could elicit significant adverse effects on the physiological functions of SAM. Exposure of pigs to aflatoxin-contaminated feed may increase their susceptibility to various secondary infections.
Asunto(s)
Aflatoxina B1/toxicidad , Lipopolisacáridos/fisiología , Macrófagos Alveolares/efectos de los fármacos , Sus scrofa/fisiología , Animales , ADN/biosíntesis , Femenino , Macrófagos Alveolares/fisiología , Masculino , Fagocitosis , Biosíntesis de Proteínas , ARN/biosíntesisRESUMEN
Outer membrane vesicles (OMVs) were isolated from an Acinetobacter strain deficient in lipopolysaccharide (LPS) due to a mutation in lpxD (IB010). Two immunizations with 10 µg of IB010 OMVs elicited total IgG, IgM, IgG1 and IgG2c titers similar to those observed after immunization with OMVs derived from the parental strain (ATCC 19606), and IB010 OMVs plus purified LPS. Immunization with IB010 OMVs resulted in significantly reduced post-infection spleen bacterial loads and serum IL-1ß and IL-6 levels compared to control mice in a disseminated sepsis model. Mice immunized with 10 µg IB010 OMVs demonstrated significant, but partial, protection (75%) against infection, whereas mice immunized with ATCC 19606 OMVs or IB010 OMVs plus purified LPS were completely protected. Immunization of mice with 100 µg of IB010 OMVs completely protected mice from infection. This study demonstrates that LPS deficient A. baumannii produces OMVs, and that immunization with these OMVs elicits protective immunity against infection.
Asunto(s)
Infecciones por Acinetobacter/prevención & control , Acinetobacter baumannii/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/administración & dosificación , Animales , Proteínas Bacterianas/genética , Vacunas Bacterianas/inmunología , Femenino , Inmunización , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Lipopolisacáridos/fisiología , Ratones , Ratones Endogámicos C57BL , Sepsis/microbiología , Sepsis/prevención & control , Bazo/microbiologíaRESUMEN
Hepatocellular carcinoma (HCC) generally occurs in the presence of chronic liver injury, often as a sequela of liver fibrosis. Hepatic progenitor cells (HPCs) are known to be capable of forming both hepatocytes and cholangiocytes in chronic liver injury, which are also considered a source of myofibroblasts and tumor-initiating cells, under carcinogenic circumstances. However, the underlying mechanisms that activate HPCs to give rise to HCC are still unclear. In current study, the correlation between HPCs activation and liver fibrosis and carcinogenesis was investigated in rats and human specimens. We analyzed the role of HPCs in tumorigenesis, by transplanting exogenous HPCs in a diethylnitrosamine-induced rat HCC model. Our data indicated that HPC activation correlated with hepatic fibrosis and hepatocarcinogenesis. We further found that exogenous HPC infusion promoted liver fibrosis and hepatocarcinogenesis, while lipopolysaccharides (LPS) played an important role in this process. However, results of our study indicated that LPS did not induce HPCs to form tumor in nude mice directly. Rather, LPS induced myofibroblast-like morphology in HPCs, which enhanced the tumorigenic potential of HPCs. Further experiments showed that LPS/Toll-like receptor 4 (TLR4) signaling mediated the differentiation of HPCs into myofibroblasts and enhanced the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which led to the aberrant expression of Ras and p53 signaling pathways in HPCs, and finally, promoted the proliferation and malignant transformation of HPCs, by long non-coding RNA regulation. Besides, examination of HCC clinical samples demonstrated that IL-6 and TNF-α production correlated with HPC activation, hepatic fibrosis, and HCC recurrence. Our study indicates that both myofibroblasts and tumor cells are derived from HPCs. HPC-derived myofibroblasts create tumor microenvironment and contribute to the proliferation and malignant transformation of HPCs. Furthermore, LPS present in the chronic liver inflammation microenvironment might play an important role in hepatocarcinogenesis, by regulating the plastic potential of HPCs.
Asunto(s)
Lipopolisacáridos/fisiología , Neoplasias Hepáticas Experimentales/etiología , Miofibroblastos/metabolismo , Células Madre/metabolismo , Microambiente Tumoral , Adulto , Anciano , Animales , Carcinogénesis , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular , Células Cultivadas , Citocinas/biosíntesis , Femenino , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones Desnudos , Persona de Mediana Edad , Miofibroblastos/citología , ARN Largo no Codificante/metabolismo , Ratas Endogámicas F344 , Transducción de Señal , Trasplante de Células Madre , Células Madre/citología , Células Madre/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Adulto JovenRESUMEN
Myeloid differentiation factor 88 (MyD88) is a universal and essential adaptor protein required for the Toll-like receptors (TLRs) pathway activation in invertebrates as well as in vertebrates. Herein, we characterized a MyD88 (Pt-MyD88) cDNA sequence in the swimming crab (Portunus trituberculatus). The Pt-MyD88 ORF is predicted to encode 469 peptides with an N-terminal death domain and a typical C-terminal TIR domain. Real-Time quantitative PCR analysis showed that the Pt-MyD88 transcriptions were constitutively expressed in hemocytes, gill, intestine, heart and muscle in normal crab. The expressions of Pt-MyD88 would be down-regulated by V. alginolyticus or LPS challenge, and be up-regulated by WSSV infection in hemocytes. Intracellular localization showed Pt-MyD88 was distributed mainly in the cytoplasm when it was over-expressed in human cell HEK293T or in Drosophila Schneider 2 (S2). Functionally, over-expression of Pt-MyD88 could either activate the NF-κB in HEK293T cells or activate the promoters of Drosophila antimicrobial peptide genes (AMPs) in S2 cell. In primary cultured hemocytes of swimming crab, after Pt-MyD88 was knocked-down by specific long double strand RNA, the expression of anti-lipopolysaccharide factor1 (ALF1), hyastatin3, crustin1 and crustin3 have been significantly inhibited, while the expression of other AMPs is normal compared to non-specific dsRNA treated cells.
Asunto(s)
Braquiuros/genética , Braquiuros/inmunología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/inmunología , Transducción de Señal , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/química , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Secuencia de Bases , Línea Celular , Regulación hacia Abajo/inmunología , Drosophila , Femenino , Células HEK293 , Hemocitos/inmunología , Humanos , Lipopolisacáridos/fisiología , Masculino , Modelos Animales , Factor 88 de Diferenciación Mieloide/química , Filogenia , Regulación hacia Arriba/inmunología , Vibrio alginolyticus/fisiología , Virus del Síndrome de la Mancha Blanca 1/fisiologíaRESUMEN
Protein kinase CK2 (CK2) is a ubiquitous serine/threonine kinase with multiple cellular functions in vertebrates including apoptosis, differentiation, proliferation, survival, tumorigenesis, signal transduction, immune regulation and inflammation. In the current study, the catalytic and regulatory subunit homologs of Litopenaeus vannamei protein kinase CK2 (LvCK2α and LvCK2ß) were cloned and characterized. LvCK2α has a full-length cDNA sequence of 1764 bp with a 1053 bp open reading frame (ORF) encoding a putative protein of 351 amino acids, which contains a typical serine/threonine kinase domain. On the other hand, LvCK2ß has a 1394 bp full-length cDNA with an ORF of 663 bp encoding a protein with 221 amino acids, which contains a Casein kinase II regulatory subunit domain. Sequence and phylogenetic analysis revealed that LvCK2 was evolutionary related with the CK2 of invertebrates. Quantitative reverse transcription PCR (RT-qPCR) analysis showed that LvCK2α and LvCK2ß transcripts were widely expressed in all shrimp tissues tested, and were both induced in hemocytes and hepatopancreas upon challenge with Vibrio parahaemolyticus, Streptoccocus iniae, lipopolysaccharide (LPS), and white spot syndrome virus (WSSV), suggesting their involvement in shrimp immune response. Moreover, RNA interference (RNAi) of LvCK2α resulted in increased hemocytes apoptosis, shown by high caspase 3/7 activity, increased number of apoptotic cells, coupled with an elevation in transcript levels of pro-apoptotic LvCaspase3 and LvCytochrome C, and a reduction in mRNA levels of pro-survival LvBcl2, LvIAP1, and LvIAP2. In addition, LvCK2α knockdown followed by V. parahaemolyticus challenge resulted in higher cumulative mortality of shrimp. Taken together, our current findings suggest that LvCK2 modulates shrimp hemocytes apoptosis as part of the innate immune response to pathogens.
Asunto(s)
Quinasa de la Caseína II/genética , Quinasa de la Caseína II/inmunología , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Penaeidae/genética , Penaeidae/inmunología , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/química , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Secuencia de Bases , Quinasa de la Caseína II/química , Perfilación de la Expresión Génica , Lipopolisacáridos/fisiología , Filogenia , Subunidades de Proteína/química , Subunidades de Proteína/genética , Subunidades de Proteína/inmunología , Alineación de Secuencia , Streptococcus iniae/fisiología , Vibrio parahaemolyticus/fisiología , Virus del Síndrome de la Mancha Blanca 1/fisiologíaRESUMEN
A cell line (PaF) derived from the fin tissue of silver pomfret (Pampus argenteus) was established and characterized in this study. The cell line has been subcultured for more than 50 times in Dulbecco's modified Eagle's medium (DMEM) containing 15% foetal bovine serum (FBS) since the initial primary culture. PaF cells grew well at temperatures from 24°C to 28°C in DMEM supplemented with 15% FBS. Partial amplification and sequence analysis of the cytochrome B gene indicated that PaF originated from silver pomfret. Cytogenetic analysis demonstrated that the modal chromosome number was 48. A significant cytopathic effect was observed in PaF cells during viral haemorrhagic septicaemia virus (VHSV) infection, and the VHSV replication was confirmed by qRT-PCR and viral titre assays. In contrast, PaF cells were resistant to red-spotted grouper nervous necrosis virus infection. Moreover, PaF cells could respond to VHSV and lipopolysaccharide treatments, as indicated by the expression of immune-related genes, TLR5 and TLR9. In conclusion, the establishment of PaF cell line will provide an appropriate in vitro tool for the study of mechanisms of pathogen-silver pomfret interaction.
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Línea Celular/fisiología , Peces , Nodaviridae/fisiología , Novirhabdovirus/fisiología , Replicación Viral , Aletas de Animales , Animales , Enfermedades de los Peces/virología , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Expresión Génica , Septicemia Hemorrágica Viral/virología , Lipopolisacáridos/fisiología , Infecciones por Virus ARN/veterinaria , Infecciones por Virus ARN/virologíaRESUMEN
Spiroplasma eriocheiris is a crustacean pathogen, without a cell wall, that causes enormous economic loss. Macrobrachium rosenbergii hemocytes are the major targets during S. eriocheiris infection. As wall-less bacteria, S. eriocheiris, its membrane protein should interact with host membrane protein directly and firstly when invaded in host cell. In this investigation, six potential hemocyte receptor proteins were identified firstly that mediate interaction between S. eriocheiris and M. rosenbergii. Among these proteins, lipopolysaccharide and ß-1, 3-glucan binding protein (MrLGBP) demonstrated to bind to S. eriocheiris using bacterial binding assays and confocal microscopy. Four spiroplasma ligand proteins for MrLGBP were isolated and identified. But, competitive assessment demonstrated that only enolase of S. eriocheiris (SeEnolase) could be a candidate ligand for MrLGBP. Subsequently, the interaction between MrLGBP and SeEnolase was confirmed by co-immunoprecipitation and co-localization in vitro. After the interaction between MrLGBP and SeEnolase was inhibited by antibody neutralization test, the virulence ability of S. eriocheiris was effectively reduced. The quantity of S. eriocheiris decreased in Drosophila S2 cells after overexpression of MrLGBP, compared with the controls. In addition, RNA interference (RNAi) knockdown of MrLGBP made M. rosenbergii more sensitive to S. eriocheiris infection. Further studies found that the immune genes, including MrLGBP and prophenoloxidase (MrproPO), MrRab7A, and Mrintegrin α1 were significantly up-regulated by SeEnolase stimulation. After SeEnolase pre-stimulation, the ability of M. rosenbergii resistance to S. eriocheiris was significantly improved. Collectively, this investigation demonstrated that MrLGBP and pathogen SeEnolase involved in mediating S. eriocheiris invasion into M. rosenbergii hemocytes.
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Proteínas Portadoras/fisiología , Hemocitos/parasitología , Lectinas/fisiología , Lipopolisacáridos/fisiología , Palaemonidae/microbiología , Spiroplasma/patogenicidad , Animales , Interacciones Huésped-Patógeno , Inmunidad Innata , Palaemonidae/inmunología , Spiroplasma/enzimología , VirulenciaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Tithonia diversifolia (Helms.) A. Gray, popularly known in Brazil as "margaridão" or "mão-de-Deus" has been used in the folk medicine as anti-inflammatory and against other illnesses in several countries. Indeed, many studies show de effect of T. diversifolia in the inflammatory process, however, any of them have demonstrated the mechanism of cell migration. AIM OF THE STUDY: The aim of this investigation was to show the in vivo and in vitro effects of T. diversifolia leaves ethanol extract on neutrophil trafficking from the blood to the inflamed tissue and on cell-derived secretion of chemical mediators, as well as, the effects on inflammatory resolution and inflammatory pain. MATERIALS AND METHODS: Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally treated with the T. diversifolia extract (0.1, 1 or 3â¯mg/kg). The leukocyte influx (optical microscopy) and the secretion of chemical mediators (TNF, IL-6, IL-1ß and CXCL1, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. Histological analysis of the pouches was performed. N-Formyl-methionine-leucine-phenylalanine-induced chemotaxis, lipopolysaccharide-induced TNF, IL-6, IL-1ß, CXCL1 and NO production, and adhesion molecule expression (CD62L and CD18, flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100⯵g/mL). The resolution of inflammation was accessed by efferocytosis assay, and the antinociceptive activity was investigated using carrageenan-induced mechanical hypersensitivity. RESULTS: The oral treatment with T. diversifolia promoted reduction in the neutrophil migration as well as the decrease in total protein, TNF, IL-1ß and CXCL1 levels in the inflamed exudate. In vitro treatment with T. diversifolia shedding of ß2 integrin expressions, without alter CD62L expression. The extract was able to increase the efferocytosis of apoptotic neutrophils, and the increase of the IL-10 and the decrease of TNF secretion. Additionally, the extract reduced the hypersensitivity induced by carrageenan. CONCLUSIONS: Together, the data herein obtained showed that T. diversifolia extract presented anti-inflammatory activity by inhibiting the cytokine and NO production, and also the leukocyte migration. The mechanisms involved in the extract anti-inflammatory effects include the impairment in the leukocyte migration to the inflamed tissue, the pro-resolution activity, and consequently the anti-hypersensitivity.
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Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Tithonia , Animales , Carragenina , Quimiotaxis de Leucocito/efectos de los fármacos , Citocinas/inmunología , Hiperalgesia/inducido químicamente , Hiperalgesia/inmunología , Lipopolisacáridos/farmacología , Lipopolisacáridos/fisiología , Masculino , Ratones , Neutrófilos/fisiología , Óxido Nítrico/metabolismo , Hojas de la Planta , Tallos de la PlantaRESUMEN
BACKGROUND: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function that leads to acute kidney injury (AKI). This study evaluated the role of lipopolysaccharide (LPS) in the development of AKI in patients with acute heart failure (AHF) and its relationship with renal parameters, to enable a better comprehension of the pathophysiology of CRS type 1. METHODS: We enrolled 32 AHF patients, 15 of whom were classified as having CRS type 1. Eight of these 15 exhibited AKI at the time of admission (caused by AHF) and the other 7 developed AKI during their stay in hospital (in the first 48 h). We evaluated the plasmatic LPS concentrations as well as conventional (serum creatinine [sCr] and urea) and unconventional (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C) renal markers. RESULTS: LPS levels were significantly higher in the CRS type 1 patients. No significant difference in LPS level was found in patients who were admitted with AKI and those developed AKI in hospital, but there was a tendency towards a higher level of LPS in CRS type 1 patients admitted with AKI. The LPS concentrations at admission were similar in CRS type 1 survivors (n = 12) and nonsurvivors (n = 3) (p = 0.22). We observed a positive correlation between LPS level and NGAL, Scr at admission and peak Scr during hospitalization and urea at admission. CONCLUSION: CRS type 1 patients present with an increased level of LPS and there is a direct correlation between LPS and renal parameters. This pilot research is the first study to explore the premise of LPS as novel pathophysiological factor in CRS type 1.
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Síndrome Cardiorrenal/sangre , Lipopolisacáridos/sangre , Enfermedad Aguda , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Síndrome Cardiorrenal/complicaciones , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Hospitalización , Humanos , Lipopolisacáridos/fisiología , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Salmonella enterica serovar Typhimurium, a Gram-negative bacterium, can cause infectious diseases ranging from gastroenteritis to systemic dissemination and infection. However, the molecular mechanisms underlying this bacterial dissemination have yet to be elucidated. A study indicated that using the lipopolysaccharide (LPS) core as a ligand, S Typhimurium was able to bind human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (hCD209a), an HIV receptor that promotes viral dissemination by hijacking antigen-presenting cells (APCs). In this study, we showed that S Typhimurium interacted with CD209s, leading to the invasion of APCs and potentially the dissemination to regional lymph nodes, spleen, and liver in mice. Shielding of the exposed LPS core through the expression of O-antigen reduces dissemination and infection. Thus, we propose that similar to HIV, S Typhimurium may also utilize APCs via interactions with CD209s as a way to disseminate to the lymph nodes, spleen, and liver to initiate host infection.
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Moléculas de Adhesión Celular/fisiología , Lectinas Tipo C/fisiología , Receptores de Superficie Celular/fisiología , Salmonella typhimurium/patogenicidad , Animales , Células Presentadoras de Antígenos/microbiología , Femenino , Interacciones Huésped-Patógeno , Humanos , Lipopolisacáridos/fisiología , Mananos/farmacología , Ratones , Ratones Endogámicos C57BL , Antígenos O/fisiología , Ganglios Linfáticos Agregados/fisiología , Fagocitosis , Células RAW 264.7RESUMEN
BACKGROUND: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury. In this study, we evaluate the role of lipopolysaccharide (LPS) and various inflammatory markers in the developing acute kidney injury (AKI) in acute heart failure (AHF) patients. METHODS: We enrolled 31 AHF patients and 20 CRS type 1 (the cause of AKI was presumed to be related to cardiac dysfunction) and 17 healthy volunteers without AHF, AKI or CKD, as control group (CTR). We assessed levels of LPS, proinflammatory cytokines (TNF-α, IL-6, IL-18), and oxidative stress marker (myeloperoxidase, MPO). RESULTS: We observed a significant increase in LPS, TNF-α, IL-6, IL-18 and MPO levels in CRS type 1 and AHF group compared to CTR. LPS levels resulted significantly higher in CRS type 1 patients compared with AHF (118.2 pg/mL, IQR 77.8-217.6 versus 13.5 pg/mL, IQR 12.0-17.0, p = 0.008). We found a cytokines and oxidative stress dysregulation in CRS type 1 patients compared with AHF. Furthermore, we observed a strong positive significant correlation between LPS levels and IL-6 (Spearman's rho = 0.79, p < 0.001), and IL-18 (Spearman's rho = 0.77, p < 0.001) and MPO (Spearman's rho = 0.80, p < 0.001), all confirm by simple linear regression analysis. CONCLUSION: CRS type 1 patients presented an increased level of LPS, pro-inflammatory cytokines, and MPO. Furthermore, there is a direct correlation between LPS and pro-inflammatory cytokines and stress oxidative marker. LPS may play a role in the pathophysiology of CRS type 1 inducing inflammation, oxidative stress and finally kidney damage.
Asunto(s)
Síndrome Cardiorrenal/sangre , Síndrome Cardiorrenal/complicaciones , Inflamación/etiología , Lipopolisacáridos/sangre , Estrés Oxidativo , Enfermedad Aguda , Lesión Renal Aguda/etiología , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Síndrome Cardiorrenal/metabolismo , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Interleucina-18/sangre , Interleucina-6/sangre , Lipopolisacáridos/fisiología , Masculino , Peroxidasa/sangre , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/sangreRESUMEN
C-type lectin has received widespread attention in animal immunomodulation functions since it was discovered, but it is still limited in crustaceans. The present study is to explore effects of one recombinant C-type lectin (LvLec protein) on haemocyte immune response in Litopenaeus vannamei (L. vannamei). The methods of keeping haemocyte immune activity were optimised by the Key Laboratory of Mariculture. The experiment was divided into four groups: control group, recombinant protein group (LvLec protein, 1.0â¯mgâ¯mL-1), Lipopolysaccharide group (LPS, 1.0â¯mgâ¯mL-1), and LPS combine with LvLec protein group (LPS + LvLec protein, 1.0â¯mgâ¯mL-1 + 1.0 mg mL-1), while each group processes 0, 3, 6, 9, 12, and 24â¯h respectively. The results showed that the haemocyte count reduced, while the exocytosis PO activity, hemagglutinating activity and phagocytic activity promoted, and the concentration of cGMP and PKA increased after LvLec protein treatment. However, the levels of antibacterial activity and bacteriolytic activity as well as the concentrations of cAMP and PKG did not change significantly after treating with LvLec protein, LPS or LPS + LvLec protein. Therefore, these results suggest that LvLec protein can stimulate the exocytosis PO activity through cGMP-PKA pathway to affect the phagocytic activity and hemagglutinating activity of L. vannamei haemocytes in vitro.
Asunto(s)
Hemocitos/inmunología , Inmunidad Innata/genética , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Penaeidae/genética , Penaeidae/inmunología , Animales , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Catecol Oxidasa/genética , Catecol Oxidasa/metabolismo , Precursores Enzimáticos/genética , Precursores Enzimáticos/metabolismo , Hemocitos/enzimología , Inmunomodulación/genética , Lipopolisacáridos/fisiología , Penaeidae/enzimología , Fagocitosis/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunologíaRESUMEN
Bactericidal permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) play important roles in host antimicrobial defense. In the present study, we identified one isoform of BPI/LBP gene from turbot (Scophthalmus maximus), designated as SmBPI/LBP1. The full-length cDNA sequence of SmBPI/LBP1 was 1826 bp, which encoding one secreted protein with 480 amino acid residues. Structurally, the SmBPI/LBP1 showed high similarity to its homologs from other vertebrates or invertebrates, which all contained a signal peptide, a BPI/LBP/CETP N-terminal with a LPS-binding domain, and a BPI/LBP/CETP C-terminal domain. The deduced amino acid sequences of SmBPI/LBP1 shared significant similarity to BPI/LBP of Seriola lalandi dorsalis (71%) and Paralichthys olivaceus (69%). Phylogentic analysis further supported that SmBPI/LBP1 act as a new member of vertebrate BPI/LBP family. SmBPI/LBP1 was ubiquitously expressed in all tested tissues, with the highest expression level in spleen tissue. The mRNA expression of SmBPI/LBP1 in spleen and kidney were significantly up-regulated after Vibrio vulnificus challenge. Finally, the recombinant SmBPI/LBP1 showed high affinity to lipopolysaccharide, followed by peptidoglycan and lipoteichoic acid, which is the ubiquitous component of Gram-negative or Gram-positive bacteria. These results indicated that SmBPI/LBP1 probably played important roles in immune response against bacteria infection.
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Enfermedades de los Peces/inmunología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Peces Planos/genética , Peces Planos/inmunología , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Proteínas de Fase Aguda/química , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/inmunología , Secuencia de Aminoácidos , Animales , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/inmunología , Secuencia de Bases , Proteínas Sanguíneas/química , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/inmunología , Proteínas Portadoras/química , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Proteínas de Peces/química , Perfilación de la Expresión Génica/veterinaria , Lipopolisacáridos/fisiología , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Peptidoglicano , Filogenia , Alineación de Secuencia/veterinaria , Ácidos Teicoicos , Vibriosis/inmunología , Vibriosis/veterinaria , Vibrio vulnificus/fisiologíaRESUMEN
The compound, 1-((4-fluorophenyl)thio)isoquinoline (FPTQ), is a synthetic isoquinoline derivative. To test the anti-inflammatory effect of FPTQ, we used neutrophil-specific transgenic zebrafish Tg(mpx::EGFP)i114 line and lipopolysaccharide (LPS)-stimulated RAW264.7â¯cells. We also used two different methods, involving tail transection and LPS stimulation in the zebrafish model. Neutrophils translocation in the zebrafish tail-transected model was inhibited by FPTQ. Neutrophil aggregation was also inhibited by FPTQ in the LPS-stimulated zebrafish model. Decreased mRNA expression of the pro-inflammatory cytokine genes, interleukin-1ß (il-1ß) and interleukin-6 (il-6), was found in zebrafish larvae injected with FPTQ. Additionally, production of nitric oxide was inhibited by FPTQ in RAW264.7 macrophage cells treated with LPS. Moreover, the mRNA expression of Il-1ß and Il-6 suppressed by FPTQ treatment in RAW264.7 macrophage cells, and an enzyme immunoassay showed that FPTQ suppressed the secretion of IL-1ß and IL-6 in RAW264.7â¯cells. These results demonstrate that FPTQ reduced inflammatory responses and, therefore, suggest that it may be effective as an anti-inflammatory agent.
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Antiinflamatorios/farmacología , Lipopolisacáridos/fisiología , Macrófagos/inmunología , Neutrófilos/inmunología , Quinolinas/farmacología , Pez Cebra/inmunología , Animales , Animales Modificados Genéticamente/inmunología , Macrófagos/efectos de los fármacos , Ratones , Neutrófilos/efectos de los fármacos , Células RAW 264.7RESUMEN
This study was carried out to investigate the protective effects of leonurine hydrochloride (LH, from Leonurus sibiricus) on lipopolysaccharide (LPS)-stimulated broiler chicks. A total of 120 one-day-old male Ross broilers were randomly divided into 4 treatment groups with 6 replicates of 5 birds per cage. The experiment was designed as a 2 × 2 factorial arrangement with LH (0 or 120 mg/kg) and LPS (injection of saline or 1.5 mg/kg body weight) levels as treatments. On days 14, 16, 18, and 20 of the trial, broilers were intraperitoneally injected with LPS or saline. Blood, spleen, and liver samples were collected on days 21 and 28 for analysis. The results showed that dietary LH had no effect on growth performance or immunoglobulin concentrations in the serum. However, dietary LH prevented LPS-induced reductions in average daily gain and average daily feed intake in the broilers on days 15-21 of the trial (P > 0.05). Dietary LH supplementation dramatically attenuated the LPS-induced increases in the spleen index, reduced glutathione (GSH) activity (serum and liver) and total superoxide dismutase (T-SOD) activity (serum and spleen), and significantly reduced malondialdehyde (MDA) levels (serum, spleen, and liver) on days 21 and 28 (P < 0.05). Additionally, LH supplementation significantly mitigated the LPS-induced increases in the tumor necrosis factor (TNF)-α (serum and spleen), interleukin (IL)-1ß (serum, spleen and liver), IL-2 (liver), IL-6 (serum, spleen and liver), toll-like receptor 4 (TLR4) (spleen and liver), and nuclear factor (NF)-κB (spleen and liver) levels on days 21 and 28 (P < 0.05). Therefore, this study revealed that LH could downregulate the expression of proinflammatory factors, mainly by inhibiting the expression of TLR4 and the activation of NF-κB. LH may be a potential feed additive with dual efficacy as an anti-inflammatory and antioxidant agent.
Asunto(s)
Pollos , Ácido Gálico/análogos & derivados , Inflamación/veterinaria , Lipopolisacáridos/fisiología , Estrés Oxidativo/efectos de los fármacos , Enfermedades de las Aves de Corral/prevención & control , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Suplementos Dietéticos/análisis , Ácido Gálico/administración & dosificación , Ácido Gálico/metabolismo , Inflamación/inmunología , Inflamación/prevención & control , Masculino , Enfermedades de las Aves de Corral/inmunologíaRESUMEN
This experiment was conducted to study the effects of orally administered carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide (LPS). Eighty 28-day-old (1.28 ± 0.15 kg) ROSS 308 broilers were assigned to a 2 × 2 factorial arrangement of treatments (20 pens of 1 chick/trt). Factors were carvacrol essential oil (orally administered or non-orally administered) and LPS (challenged or non-challenged). Individually housed broilers were randomly assigned (n = 20 broilers per treatment: 10 males and 10 females) to four treatments: (1) basic diet (CTR), (2) basic diet + carvacrol (CAR), (3) basic diet + LPS-challenge (LPS), (4) basic diet + carvacrol + LPS-challenge (CAR+LPS). All were fed with the same diet. The experimental period was for 15 d, after which injecting LPS significantly up-regulated the gene expression levels of TNF-α (P < 0.05), IL-1ß (P < 0.05), IL-6 (P < 0.05), IL-8 (P < 0.05), TLR2 (P < 0.05), TLR4 (P < 0.05), NF-κB p65 (P < 0.05), AVBD-9 (P < 0.05), and SIgA(P < 0.05) compared with the CTR group; the broilers were challenged by LPS after oral administration of carvacrol, they had significant lower on the gene expression levels of TNF-α (P < 0.05), IL-1ß (P < 0.05), IL-6 (P < 0.05), TLR4 (P < 0.05), NF-κB p65 (P < 0.05), and AVBD-9 (P < 0.05) than the LPS group. In conclusion, the broilers orally administrated carvacrol essential oils inhibited the secretion of inflammatory cytokines caused by LPS, affected the pathway of TLRs/NF-κB, and showed an anti-inflammatory function.
Asunto(s)
Antiinflamatorios/farmacología , Pollos , Citocinas/genética , Inflamación/veterinaria , Monoterpenos/farmacología , Aceites Volátiles/farmacología , Enfermedades de las Aves de Corral/inmunología , Administración Oral , Animales , Antiinflamatorios/administración & dosificación , Proteínas Aviares/genética , Proteínas Aviares/metabolismo , Cimenos , Citocinas/metabolismo , Femenino , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Inflamación/inducido químicamente , Inflamación/inmunología , Lipopolisacáridos/fisiología , Masculino , Monoterpenos/administración & dosificación , Aceites Volátiles/administración & dosificación , Enfermedades de las Aves de Corral/inducido químicamente , Distribución AleatoriaRESUMEN
Cell-to-cell signaling via small molecules is an essential process to coordinate behavior in single species within a community, and also across kingdoms. In this review, we discuss the quorum sensing (QS) systems used by the opportunistic pathogen Pseudomonas aeruginosa to sense bacterial population density and fitness, and regulate virulence, biofilm development, metabolite acquisition, and mammalian host defense. We also focus on the role of N-acylhomoserine lactone-dependent QS signaling in the modulation of innate immune responses connected together via calcium signaling, homeostasis, mitochondrial and cytoskeletal dynamics, and governing transcriptional and proteomic responses of host cells. A future perspective emphasizes the need for multidisciplinary efforts to bring current knowledge of QS into a more detailed understanding of the communication between bacteria and host, as well as into strategies to prevent and treat P. aeruginosa infections and reduce the rate of antibiotic resistance.