RESUMEN
Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patient. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with CCL18 to induced CD8+ TRM cell expansion and exacerbated fibrosis, while blocking CCR8 prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach.
RESUMEN
Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling.
Asunto(s)
Asma , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Ratas , Animales , Remodelación de las Vías Aéreas (Respiratorias) , Fenotipo Secretor Asociado a la Senescencia , Miocitos del Músculo Liso , Asma/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Colágeno Tipo I , Proliferación Celular , Material Particulado/metabolismo , Células CultivadasRESUMEN
A regioselective metal-free sulfenylation of imidazoheterocycles with heterocyclic thiols or thiones has been achieved using a cross-dehydrogenative coupling method in water. In addition, the procedure has several advantages including green solvents, free of foul-smelling sulfur sources, and mild conditions, thus providing considerable application potential in the pharmaceutical industry.
Asunto(s)
Industria Farmacéutica , Agua , Solventes , Compuestos de Sulfhidrilo , AzufreRESUMEN
Stem cell therapy is a promising strategy for tissue regeneration. The therapeutic benefits of cell therapy are mediated by both direct and indirect mechanisms. However, the application of stem cell therapy in the clinic is hampered by several limitations. This concise review provides a brief introduction into stem cell therapies for ischemic heart disease. It summarizes cell-based and cell-free paradigms, their limitations, and the benefits of using them to target disease. Stem Cells Translational Medicine 2018;7:354-359.
Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Corazón/fisiología , Células Madre/citología , Animales , Cardiopatías/terapia , Humanos , Regeneración/fisiología , Trasplante de Células Madre/métodosRESUMEN
A novel transcript of human HPO (HPO-205) encoding a 205 amino acid ORF corresponding to a translated product of 23 kD different from the previous HPO that lacks the N-terminal 80 amino acids, was isolated from human fetal liver cDNA library by 5'RACE methods. The dose-dependent stimulation of DNA synthesis of HepG2 hepatoma cells by HPO-205 demonstrated its similar biological activity with HPO in vitro. The level of MAPK (mitogen-activated protein kinase)phosphorylation was further examined by Western blot analysis and the result revealed that HPO-205 protein might have stronger activity on stimulating hepatic cell proliferation than that of HPO. The similar result was observed by FACS technique. Therefore, our results suggest that the HPO-205 has activity to stimulate proliferation of liver derived cells, and this activity may be stronger than HPO.
Asunto(s)
Factor de Crecimiento de Hepatocito/farmacología , ARN/genética , Secuencia de Aminoácidos , Animales , Western Blotting , Células COS , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , ADN Complementario/química , ADN Complementario/genética , Relación Dosis-Respuesta a Droga , Expresión Génica , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Datos de Secuencia Molecular , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacología , ARN/aislamiento & purificación , ARN/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Transcripción Genética , Células Tumorales CultivadasRESUMEN
AIM: To isolate a novel isoform of human HPO (HPO-205) from human fetal liver Marathon-ready cDNA and characterize its primary biological function. METHODS: 5'-RACE (rapid amplification of cDNA 5' ends) was used to isolate a novel isoform of hHPO in this paper. The constructed pcDNA(HPO-205), pcDNA(HPO) and pcDNA eukaryotic expression vectors were respectively transfected by lipofectamine method and the stimulation of DNA synthesis was observed by (3)H-TdR incorporation assay. Proteins extracted from different cells were analyzed by Western blot. RESULTS: A novel isoform of hHPO (HPO-205) encoding a 205 amino acid ORF corresponding to a translated production of 23 kDa was isolated and distinguished from the previous HPO that lacked the N-terminal 80 amino acids. The dose-dependent stimulation of DNA synthesis of HepG2 hepatoma cells by HPO-205 demonstrated its similar biological activity with HPO in vitro. The level of MAPK (Mitogen-activated protein kinase) phosphorylation by Western blot analysis revealed that HPO-205 might have the stronger activity of stimulating hepatic cell proliferation than that of HPO. CONCLUSION: A novel isoform of hHPO (HPO-205) was isolated from hepatic-derived cells. The comparison of HPO-205 and HPO will lead to a new insight into the structure and function of hHPO, and provide the new way of thinking to deeply elucidate the biological roles of HPO/ALR.