RESUMEN
Staphylococcus aureus (S. aureus) is an important zoonotic food-borne pathogen causing severe invasive infections, such as sepsis, pneumonia, food poisoning, toxic shock syndrome and autoimmune diseases. Staphylococcal enterotoxin O (SEO) is a new type of enterotoxins of S. aureus with superantigenic and emetic activity. However, it is still unclear about SEO-induced host inflammatory response. Therefore, the mechanism of SEO-induced interleukin-1ß (IL-1ß) secretion in mouse neutrophils was investigated in this study. Our results showed that recombinant SEO had superantigenic activity with high level of gamma interferon (IFN-γ) production in mouse spleen cells and induced inflammatory cytokines expression including IL-1α, IL-1ß, IL-6 and TNF-α in neutrophils under the action of ATP. In addition, SEO-induced IL-1ß secretion was dependent on activation of Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways. However, SEO-induced IL-1ß secretion was abolished in the neutrophils of NLRP3-/- mice compared with those of wild type mice, indicating that activation of NLRP3 inflammasome mediated IL-1ß secretion during neutrophils stimulation with SEO under the action of ATP. Moreover, this process of SEO+ATP-induced IL-1ß secretion was dependent on potassium (K+) efflux. Taken together, our study suggests that activation of TLR4/JNK/NLRP3 inflammasome signaling pathway mediate maturation and secretion of IL-1ß and provides a new insight on S. aureus virulence factor-induced host immune response.
Asunto(s)
Adenosina Trifosfato/metabolismo , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neutrófilos/inmunología , Infecciones Estafilocócicas/inmunología , Animales , Modelos Animales de Enfermedad , Enterotoxinas/inmunología , Humanos , Inflamasomas/genética , Inflamasomas/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Sistema de Señalización de MAP Quinasas/inmunología , Ratones , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Neutrófilos/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/inmunología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factores de Virulencia/inmunologíaRESUMEN
Salmonella is considered one of the leading causes for foodborne diseases in humans. Pork and its products contaminated with Salmonella are increasingly recognized as an important source of human salmonellosis. The aim of this study was to investigate the antimicrobial resistance and prevalence of integrons in Salmonella isolates from pig farms. In total, 92 of 724 (12.7%) samples were Salmonella-positive, including 64 (15.0%) from fecal samples, 27 (12.6%) from floor samples, 1 (4.5%) from water samples, and 0 from feed and air samples. These isolates showed the highest resistance to tetracycline (85.9%), followed by trimethoprim (67.4%), ampicillin (60.9%), and chloramphenicol (51.1%). In addition, 51 isolates carried the complete class 1 integron, most of which (42/51) harbored antibiotic resistance cassettes. A total of six gene cassettes including orfF, est-X, dfrA1+aadA1, aadA1, dfrA12+aadA2, and sat were identified, in which the most prevalent one was orfF (29.4%). Furthermore, all 19 class 1 integron-positive isolates harboring dfr genes showed resistance to trimethoprim (SXT), suggesting that the trimethoprim resistance gene (dfr) may contribute to the emergence of SXT resistance phenotype. Therefore, considering the significance of integrons and related resistance genes for public health, special measures should be taken to control Salmonella spp. on the pig farms and to prevent spread of integrons and associated resistance genes.
Asunto(s)
Antibacterianos , Integrones , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana Múltiple/genética , Granjas , Integrones/genética , Salmonella/genética , PorcinosRESUMEN
Staphylococcus aureus is a Gram-positive opportunistic pathogen which causes infections in a variety of vertebrates. Virulence factors are the main pathogenesis of S. aureus as a pathogen, which induce the host's innate and adaptive immune responses. Toxic shock syndrome toxin 1 (TSST-1) is one of the most important virulence factors of S. aureus. However, the role of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) in TSST-1-induced innate immune response is still unclear. Here, purified recombinant TSST-1 (rTSST-1) was prepared and used to stimulate mouse peritoneal macrophages. The results showed that under the action of adenosine-triphosphate (ATP), rTSST-1 significantly induced interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) production in mouse macrophages and the production was dose-dependent. In addition, rTSST-1+ATP-stimulated cytokine production in macrophage depends on the activation of toll like receptor 4 (TLR4), but not TLR2 on the cells. Furthermore, the macrophages of NLRP3-/- mice stimulated with rTSST-1+ATP showed significantly low levels of IL-1ß production compared to that of wild-type mice. These results demonstrated that TSST-1 can induce the expression of inflammatory cytokines in macrophages via the activation of the TLR4 and NLRP3 signaling pathways. Our study provides new information about the mechanism of the TSST-1-inducing host's innate immune responses.
Asunto(s)
Toxinas Bacterianas/inmunología , Citocinas/inmunología , Enterotoxinas/inmunología , Inflamasomas/inmunología , Macrófagos Peritoneales/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Superantígenos/inmunología , Animales , Proteínas Bacterianas/inmunología , Relación Dosis-Respuesta a Droga , Interacciones Huésped-Patógeno , Inmunidad Innata , Interleucina-1beta/inmunología , Ratones , Ratones Noqueados , Proteínas Recombinantes/inmunología , Transducción de Señal , Staphylococcus aureus/inmunología , Receptor Toll-Like 4/inmunología , Factores de Virulencia/inmunologíaRESUMEN
INTRODUCTION: Integrons are mobile DNA elements that allow for acquisition and dissemination of antibiotic-resistance genes among pig farm-derived bacteria. Limited information is available on integrons of Staphylococcus aureus from pig farms. The aim of this study was to characterise and investigate the prevalence of class 1 and 2 integrons in multi-drug resistant (MDR) S. aureus isolates from pig farms. MATERIAL AND METHODS: A total of 724 swabs were collected from 12 pig farms in Chongqing, China, and examined by conventional microbial and molecular methods. RESULTS: In total, 68 isolates were S. aureus, 57 of which were methicillin resistant (MRSA). All 68 isolates were MDR strains and carried integrons, of which 88.2% (60/68) harboured both class 1 and 2. In addition, 85.3% (58/68) of the class 2 integron-positive isolates carried the ß-lactam resistance gene (blaTEM-1 ), and 66.7% (40/60) of the class 1 integron-positive isolates carried the aadA1c, aadA1 or dfrA1 gene for respective streptomycin and spectinomycin or trimethoprim resistance. CONCLUSIONS: Class 1 and 2 integrons are common among the pig farm-derived S. aureus isolates. On account of their significance for public health, the prevalence of the integrons and their associated resistance genes in pig farm-derived S. aureus isolates should be paid special attention.
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Proteínas de Unión al ADN/fisiología , Inflamasomas/metabolismo , Infecciones Neumocócicas/inmunología , Animales , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/metabolismo , Caspasa 1/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Dimerización , Inflamasomas/genética , Interleucina-1beta/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/microbiología , Pulmón/patología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
Enzootic nasal adenocarcinoma (ENA) of goats, characterized by transformation of epithelial cells of the ethmoid turbinates, is caused by enzootic nasal tumor virus 2 (ENTV-2). ENTV-2 belongs to the genus Betaretrovirus and has extended its distribution globally with a high prevalence; however, the genetic diversity and genotypic distribution for ENTV-2 have not been analyzed systematically due to the limited availability of sequence data. In this study, an infection by ENTV-2 was detected by RT-PCR in Chongqing in July 2018, and the complete sequence of one strain (CQ1) was determined. Phylogenetic analysis indicated a high degree of genetic heterogeneity among ENTV-2 sequences, with the existence of two main lineages. Lineage 1 and 2 were composed of ENTV-2 from China and the UK, respectively. Although CQ1 was closely related to recent ENTV-2 strains collected in the neighboring provinces of Chongqing (Shaanxi and Sichuan), it formed a separate sublineage of lineage 1 (sublineage 1.3). This report will enhance our understanding of the epidemiology of ENTV-2 in China.
Asunto(s)
Betaretrovirus/clasificación , Técnicas de Genotipaje/métodos , Enfermedades de las Cabras/virología , Neoplasias Nasales/veterinaria , Análisis de Secuencia de ARN/métodos , Animales , Betaretrovirus/genética , Betaretrovirus/aislamiento & purificación , China , Variación Genética , Cabras , Neoplasias Nasales/virología , Filogenia , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Reino UnidoRESUMEN
Inhibitory neurotransmission in amygdala is important for fear learning and memory. However, mechanisms that control the inhibitory activity in amygdala are not well understood. We provide evidence that neuregulin 1 (NRG1) and its receptor ErbB4 tyrosine kinase are critical for maintaining GABAergic activity in amygdala. Neutralizing endogenous NRG1, inhibition, or genetic ablation of ErbB4, which was expressed in a majority of palvalbumin (PV)+ neurons in amygdala, reduced GABAergic transmission and inhibited tone-cued fear conditioning. Specific ablation of ErbB4 in PV+ neurons reduced eIPSC/eEPSC ratios and impaired fear conditioning. Notably, expression of ErbB4 in amygdala was sufficient to diminish synaptic dysfunction and fear conditioning deficits in PV-ErbB4-/- mice. These observations indicated that NRG1 signaling maintains high GABAergic activity in amygdala and, thus, regulates fear memory. Considering that both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study sheds light on potential pathophysiological mechanisms of this disorder.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Miedo/fisiología , Memoria/fisiología , Neurregulina-1/metabolismo , Receptor ErbB-4/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Condicionamiento Clásico/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Potenciales Postsinápticos Inhibidores/fisiología , Interneuronas/fisiología , Ratones , Neuronas/metabolismo , Parvalbúminas/metabolismo , Sinapsis/fisiologíaAsunto(s)
Glutatión/uso terapéutico , Guanidinas/uso terapéutico , Poscondicionamiento Isquémico/métodos , Daño por Reperfusión Miocárdica/prevención & control , Intercambiadores de Sodio-Hidrógeno/antagonistas & inhibidores , Sulfonas/uso terapéutico , Animales , Masculino , Daño por Reperfusión Miocárdica/fisiopatología , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Paeoniflorin is one of the bioactive components of Paeonia lactiflora, a traditional Chinese herbal medicine. It is the main monoterpene glucoside isolated from the P. lactiflora in 1963. Since then, researchers have found that paeoniflorin has multifold pharmacological effects. In this review, based on the recent available papers published in PubMed and National Knowledge Infrastructure Data Base, we present the major current approaches in understanding the detection methodology, pharmacokinetics and pharmacology, and toxicology of paeoniflorin.
Asunto(s)
Benzoatos , Hidrocarburos Aromáticos con Puentes , Medicamentos Herbarios Chinos , Glucósidos , Animales , Benzoatos/análisis , Benzoatos/farmacocinética , Benzoatos/farmacología , Hidrocarburos Aromáticos con Puentes/análisis , Hidrocarburos Aromáticos con Puentes/farmacocinética , Hidrocarburos Aromáticos con Puentes/farmacología , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Ensayo de Inmunoadsorción Enzimática , Glucósidos/análisis , Glucósidos/farmacocinética , Glucósidos/farmacología , Humanos , MonoterpenosRESUMEN
Transient forebrain ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms are as yet unclear, but it is known that activation of L-type Ca2+ channels specifically increases the expression of a group of genes required for neuronal survival. Accordingly, we examined temporal changes in L-type calcium-channel activity in CA1 and CA3 pyramidal neurons of rat hippocampus after transient forebrain ischemia by patch-clamp techniques. In vulnerable CA1 neurons, L-type Ca2+-channel activity was persistently downregulated after ischemic insult, whereas in invulnerable CA3 neurons, no change occurred. Downregulation of L-type calcium channels was partially caused by oxidation modulation in postischemic channels. Furthermore, L-type but neither N-type nor P/Q-type Ca2+-channel antagonists alone significantly inhibited the survival of cultured hippocampal neurons. In contrast, specific L-type calcium-channel agonist remarkably reduced neuronal cell death and restored the inhibited channels induced by nitric oxide donor. More importantly, L-type calcium-channel agonist applied after reoxygenation or reperfusion significantly decreased neuronal injury in in vitro oxygen-glucose deprivation ischemic model and in animals subjected to forebrain ischemia-reperfusion. Together, the present results suggest that ischemia-induced inhibition of L-type calcium currents may give rise to delayed death of neurons in the CA1 region, possibly via oxidation mechanisms. Our findings may lead to a new perspective on neuronal death after ischemic insult and suggest that a novel therapeutic approach, activation of L-type calcium channels, could be tested at late stages of reperfusion for stroke treatment.