RESUMEN
The aim of this study was to observe the effect of interleukin (IL)-17 on early immune response and inflammation in the lungs of respiratory syncytial virus (RSV)-infected mice. Specific pathogen-free BALB/c mice were randomly assigned to control, RSV-infected, RSV-infected with phosphate-buffered saline, and RSV-infected + IL-17 intervention groups. The RSV infection model was set up by nasal mucosa immunization. The intervention group was provided with restructured IL-17 (intranasal). The viral load and cytokine concentrations in the lung tissues and broncho-alveolar lavage fluid (BALF) were determined by real-time-polymerase chain reaction and enzyme-linked immunosorbent assay. RSV caused acute lung inflammation in mice with a significantly higher number of neutrophils and cytokines such as interferon-gamma (IFN-γ), IL-1ß, IL-6, and G-CSF in the BALF than that in the control group. IL-17 intervention led to a significant increase in the number of neutrophilic granulocytes in the BALF. Alternately, IL-17 intervention led to a significant decrease in the IFN-γ concentration and a significant increase in the IL-1ß, IL-6 and G-CSF levels in the BALF. IL-17 induced a reduction in the viral load and an increase in the survival rate of mice on the third day of infection. IL- 17 mucosal immunity enhances the removal of RSV and strengthens the immune defense by promoting neutrophil migration and reducing the IFN-γ levels in mouse lungs.
Asunto(s)
Interferón gamma/metabolismo , Interleucina-17/uso terapéutico , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Virus Sincitiales Respiratorios/efectos de los fármacos , Virus Sincitiales Respiratorios/patogenicidad , Animales , Factor Estimulante de Colonias de Granulocitos/metabolismo , Interleucina-6/metabolismo , Pulmón/virología , Masculino , Ratones , Ratones Endogámicos ICR , Neutrófilos/metabolismo , Infecciones por Virus Sincitial Respiratorio/metabolismoRESUMEN
Tissue engineering encapsulated cells such as chondrocytes in the carrier matrix have been widely used to repair cartilage defects. However, chondrocyte phenotype is easily lost when chondrocytes are expanded in vitro by a process defined as “dedifferentiation”. To ensure successful therapy, an effective pro-chondrogenic agent is necessary to overcome the obstacle of limited cell numbers in the restoration process, and dedifferentiation is a prerequisite. Gallic acid (GA) has been used in the treatment of arthritis, but its biocompatibility is inferior to that of other compounds. In this study, we modified GA by incorporating sulfamonomethoxine sodium and synthesized a sulfonamido-based gallate, JJYMD-C, and evaluated its effect on chondrocyte metabolism. Our results showed that JJYMD-C could effectively increase the levels of the collagen II, Sox9, and aggrecan genes, promote chondrocyte growth, and enhance secretion and synthesis of cartilage extracellular matrix. On the other hand, expression of the collagen I gene was effectively down-regulated, demonstrating inhibition of chondrocyte dedifferentiation by JJYMD-C. Hypertrophy, as a characteristic of chondrocyte ossification, was undetectable in the JJYMD-C groups. We used JJYMD-C at doses of 0.125, 0.25, and 0.5 µg/mL, and the strongest response was observed with 0.25 µg/mL. This study provides a basis for further studies on a novel agent in the treatment of articular cartilage defects.
Asunto(s)
Animales , Conejos , Benzamidas/síntesis química , Desdiferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Fenotipo , Pirimidinas/síntesis química , Agrecanos/genética , Agrecanos/metabolismo , Antiinfecciosos/química , Antiinfecciosos/farmacología , Benzamidas/farmacología , Supervivencia Celular , Desdiferenciación Celular/inmunología , Condrocitos/citología , Condrocitos/metabolismo , Condrogénesis/efectos de los fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Glicosaminoglicanos/análisis , Inmunohistoquímica , Citometría de Barrido por Láser , Cultivo Primario de Células , Pirimidinas/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Ingeniería de TejidosRESUMEN
Tissue engineering encapsulated cells such as chondrocytes in the carrier matrix have been widely used to repair cartilage defects. However, chondrocyte phenotype is easily lost when chondrocytes are expanded in vitro by a process defined as "dedifferentiation". To ensure successful therapy, an effective pro-chondrogenic agent is necessary to overcome the obstacle of limited cell numbers in the restoration process, and dedifferentiation is a prerequisite. Gallic acid (GA) has been used in the treatment of arthritis, but its biocompatibility is inferior to that of other compounds. In this study, we modified GA by incorporating sulfamonomethoxine sodium and synthesized a sulfonamido-based gallate, JJYMD-C, and evaluated its effect on chondrocyte metabolism. Our results showed that JJYMD-C could effectively increase the levels of the collagen II, Sox9, and aggrecan genes, promote chondrocyte growth, and enhance secretion and synthesis of cartilage extracellular matrix. On the other hand, expression of the collagen I gene was effectively down-regulated, demonstrating inhibition of chondrocyte dedifferentiation by JJYMD-C. Hypertrophy, as a characteristic of chondrocyte ossification, was undetectable in the JJYMD-C groups. We used JJYMD-C at doses of 0.125, 0.25, and 0.5 µg/mL, and the strongest response was observed with 0.25 µg/mL. This study provides a basis for further studies on a novel agent in the treatment of articular cartilage defects.