RESUMEN
Macrophages play a crucial role in the progression of atherosclerotic lesions. In the current study, we analyzed the expression and function of sestrin1 (SESN1) in the aorta macrophages in a murine atherosclerosis model. We identified high SESN1 expression in the aorta macrophages in atherosclerotic mice. Using lentivirus-mediated SESN1 overexpression in macrophages, we found that SESN1 inhibited oxidized low-density lipoprotein-induced NLRP3 inflammasome activation in lipopolysaccharide (LPS)-primed macrophages, as evidenced by less ASC-NLRP3 complex formation, lower caspase-1 activation, and lower generation of mature IL-1ß. Besides, SESN1 impeded oxidized low-density lipoprotein-induced activation of NK-κB signaling in macrophages. Furthermore, SESN1 suppressed cholesterol crystal-induced NLRP3 inflammasome activation and foam cell formation. Adoptive transfer of SESN1 overexpressing macrophages reduced the expression of pro-inflammatory cytokines in infiltrating macrophages and the whole aorta tissue. Adoptive transfer of SESN1 knockdown macrophages enhanced the expression of pro-inflammatory cytokines in infiltrating macrophages and the whole aorta tissue. Overall, our study sheds light on the significance of SESN1 for macrophage-mediated aorta inflammation.
Asunto(s)
Aterosclerosis/etiología , Proteínas de Ciclo Celular/fisiología , Inflamasomas/fisiología , Lipoproteínas LDL/antagonistas & inhibidores , Macrófagos/fisiología , Proteína con Dominio Pirina 3 de la Familia NLR/fisiología , Animales , Aortitis/etiología , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/fisiología , Transducción de Señal/fisiologíaRESUMEN
The function of CD4+CD25+regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-β1 and IFN-γ) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P<0.01), the in- hibitory ability of Treg on the T lymphocytes proliferation was reduced (P<0.01), IFN-γ, levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvas- tatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were signifi- cantly increased in ACS patients. Serum IFN-γ, was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory ef- fects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restora- tion of immune homeostasis.
RESUMEN
With the human development and social progress,the task of reform in educa-tion and teaching has become more urgent and increasingly heavy. The article discusses the education reform of clinical medicine in the content of courses,construction of teaching materials, teaching methods,teaching assessment and teaching management areas,in combination with the pracice of the current clinical teaching reform in medical school.
RESUMEN
This article discussed how to separate examination from teaching but at the same time prevent the content of examination being out of joint with teaching when developing the warehouse and review course wares of the examination of emergency medical science,as well as how to make use of a computer to manage the warehouse and review course wares of emergency call medical science examination.
RESUMEN
AIM: To examine whether tolerogenic dendritic cells(DC) loaded with heat shock protein 60(HSP60) could restore endothelial function in hypercholesterolemic apolipoprotein E(apoE)-null mice.METHODS: Bone marrow derived DC of the mice was loaded with HSP60 and co-cultured with rapamycin to generate tolerogenic DC.The tolerogenic DC,DC loaded only with HSP60(DChsp) and saline were injected into the apoE-null mice at 6 weeks of age for two times at a one-week interval.C57BL/6 mice at the same age were taken as normal control two weeks after the last injection.Aorta was harvested for ex vivo vascular ring tension test.Immune parameters were also analyzed in vitro and in vivo.RESULTS: Compared with the non loaded DC,HSP60 pulsed DC expressed higher levels of CD86,and stimulated T lymphocytes to proliferation significantly,while the tolerogenic DC expressed lower levels of CD86,and inhibited T lymphocytes to proliferation.After immunization with different injection,Ach-induced relaxation was reduced significantly in(DChsp) group compared with saline group(P