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1.
Exp Mol Med ; 47: e171, 2015 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-26138903

RESUMEN

Pentraxin 3 (PTX3) was identified as a marker of the inflammatory response and overexpressed in various tissues and cells related to cardiovascular disease. Honokiol, an active component isolated from the Chinese medicinal herb Magnolia officinalis, was shown to have a variety of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on palmitic acid (PA)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and to elucidate potential regulatory mechanisms in this atherosclerotic cell model. Our results showed that PA significantly accelerated the expression of PTX3 in HUVECs through the IκB kinase (IKK)/IκB/nuclear factor-κB (NF-κB) pathway, reduced cell viability, induced cell apoptosis and triggered the inflammatory response. Knockdown of PTX3 supported cell growth and prevented apoptosis by blocking PA-inducted nitric oxide (NO) overproduction. Honokiol significantly suppressed the overexpression of PTX3 in PA-inducted HUVECs by inhibiting IκB phosphorylation and the expression of two NF-κB subunits (p50 and p65) in the IKK/IκB/NF-κB signaling pathway. Furthermore, honokiol reduced endothelial cell injury and apoptosis by regulating the expression of inducible NO synthase and endothelial NO synthase, as well as the generation of NO. Honokiol showed an anti-inflammatory effect in PA-inducted HUVECs by significantly inhibiting the generation of interleukin-6 (IL-6), IL-8 and monocyte chemoattractant protein-1. In summary, honokiol repaired endothelial dysfunction by suppressing PTX3 overexpression in an atherosclerotic cell model. PTX3 may be a potential therapeutic target for atherosclerosis.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Compuestos de Bifenilo/farmacología , Proteína C-Reactiva/genética , Medicamentos Herbarios Chinos/farmacología , Quinasa I-kappa B/inmunología , Lignanos/farmacología , Proteínas Serina-Treonina Quinasas/inmunología , Componente Amiloide P Sérico/genética , Apoptosis/efectos de los fármacos , Aterosclerosis/inducido químicamente , Aterosclerosis/inmunología , Aterosclerosis/patología , Compuestos de Bifenilo/química , Compuestos de Bifenilo/aislamiento & purificación , Proteína C-Reactiva/inmunología , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Células Endoteliales de la Vena Umbilical Humana , Humanos , Lignanos/química , Lignanos/aislamiento & purificación , Magnolia/química , Ácido Palmítico , Componente Amiloide P Sérico/inmunología , Transducción de Señal/efectos de los fármacos , Quinasa de Factor Nuclear kappa B
2.
Reumatismo ; 64(6): 380-7, 2012 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-23285482

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disease involving many organ systems. Glomerulonephritis (GLN) is one of the major causes of morbidity and mortality in SLE. It has recently been demonstrated that adjuvants of vaccines could cause the so called ASIA syndrome. The study aimed to assess the effects of Complete Freund's Adjuvant (CFA) vs alum injections in NZB/NZWF1 mice. Mice (n=10 each group) were injected with a total volume of 200 µL of: CFA in PBS (group 1), alum in PBS (group 2), PBS (group 3) as controls, PTX3/CFA (group 4), PTX3/alum (group 5), 3 times, 3 weeks apart /given in each injection, three weeks apart from ten weeks of age. Urine samples were collected weekly to evaluate proteinuria. Blood samples were collected before every injection, at 21 weeks of age, and at death to evaluate levels of anti-PTX3 and anti-dsDNA. Proteinuria free survival and survival rates were analyzed by the Kaplan-Meier method using Mantel-Cox's test for comparisons. CFA-treated mice developed both anti-dsDNA antibodies and proteinuria earlier and at higher levels than alumtreated and PBS-injected mice, starting from 13 weeks of age. Proteinuria free survival rates (proteinuria ≥ 300 mg/dL) and survival rates were lower in CFA-treated mice than those treated with alum or injected with PBS (P<0.001 for all). No difference was observed between the alum-treated group and PBS-injected mice. Notably, groups 4 and 5, immunized with PTX3, developed anti-PTX3 antibodies and no significant difference was observed. Alum seems to be as effective as and safer than CFA as adjuvant, since it did not affect disease progression in immunized NZB/NZWF1 mice.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Compuestos de Alumbre/administración & dosificación , Proteína C-Reactiva/inmunología , Componente Amiloide P Sérico/inmunología , Vacunación/métodos , Adyuvantes Inmunológicos/toxicidad , Compuestos de Alumbre/toxicidad , Animales , Anticuerpos Antinucleares/sangre , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Proteína C-Reactiva/administración & dosificación , ADN/inmunología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/toxicidad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/inducido químicamente , Nefritis Lúpica/inmunología , Nefritis Lúpica/orina , Ratones , Ratones Endogámicos NZB , Proteinuria/etiología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , Componente Amiloide P Sérico/administración & dosificación , Síndrome , Vacunación/efectos adversos
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