RESUMEN
The aim of this study was to explore the relationship between adiponectin (ADPN) and hemorrhagic shock (HS) and the recovery after HS. This is significant for further understanding of the pathophysiological processes of HS and the development of better treatments. In total, 72 male C57BL/6 mice were assigned randomly to three groups: control, HS, and recovery (N = 24). The HS mouse model was constructed by hemorrhage of the carotid artery and recovery was achieved by tail vein injection of Ringer's solution. The level of ADPN in the peripheral blood of mice before and after recovery was detected by enzyme-linked immunosorbent assay. Compared to control, HS mice showed significantly decreased ADPN levels with the extension of HS time while the level of ADPN in recovery mice increased significantly and remained high. The variation of ADPN levels was closely associated with the occurrence of HS in mice and their recovery, suggesting that ADPN might act as a biomarker of inflammation and have potential for the treatment of HS.
Asunto(s)
Adiponectina/sangre , Modelos Animales de Enfermedad , Inflamación , Recuperación de la Función , Choque Hemorrágico/sangre , Adiponectina/inmunología , Animales , Biomarcadores , Arterias Carótidas/metabolismo , Arterias Carótidas/fisiopatología , Masculino , Ratones , Choque Hemorrágico/inmunología , Choque Hemorrágico/metabolismo , Choque Hemorrágico/fisiopatologíaRESUMEN
RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered. OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling. METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P<0.01). AdipoR1-KD markedly reduced globular adiponectin-induced nCDase activation, whereas AdipoR2-KD only slightly reduced. More importantly, small interfering RNA-mediated nCDase-KD markedly blocked the effect of adiponectin on TNFα-induced intercellular adhesion molecule-1 expression. AMP-activated protein kinase-KD failed to block adiponectin-induced nCDase activation and modestly inhibited adiponectin anti-inflammatory effect. In contrast, in caveolin-1 KD (Cav1-KD) cells, >87% of adiponectin-induced nCDase activation was lost. Whereas adiponectin treatment failed to inhibit TNFα-induced intercellular adhesion molecule-1 expression, treatment with sphingosine-1-phosphate or SEW (sphingosine-1-phosphate receptor agonist) remained effective in Cav1-KD cells. AdipoR1 and Cav1 colocalized and coprecipitated in human umbilical vein endothelial cells. Adiponectin treatment did not affect this interaction. There is weak basal Cav1/nCDase interaction, which significantly increased after adiponectin treatment. Knockout of AdipoR1 or Cav1 abolished the inhibitory effect of adiponectin on leukocyte rolling and adhesion in vivo. CONCLUSIONS: These results demonstrate for the first time that adiponectin inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-dependent fashion.
Asunto(s)
Adiponectina/metabolismo , Caveolina 1/metabolismo , Ceramidasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Vasculitis/metabolismo , Adiponectina/inmunología , Caveolina 1/genética , Caveolina 1/inmunología , Ceramidasas/genética , Ceramidasas/inmunología , Células Endoteliales/inmunología , Activación Enzimática/inmunología , Técnicas de Silenciamiento del Gen , Células Endoteliales de la Vena Umbilical Humana , Humanos , Rodamiento de Leucocito/inmunología , ARN Interferente Pequeño/genética , Especies de Nitrógeno Reactivo/inmunología , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/inmunología , Receptores de Adiponectina/metabolismo , Transducción de Señal/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Vasculitis/inmunologíaRESUMEN
Nos últimos anos têm sido descritos mediadores sintetizados no tecido adiposo, chamados adipocinas. Eles apresentam ação hormonal, regulando o apetite e o metabolismo da glicose, mas também atuam como citocinas, com efeitos sobre o sistema imune, incluindo efeitos na autoimunidade. As adipocinas mais importantes são: leptina, adiponectina, visfatina e resistina. Algumas delas vêm sendo estudadas nas doenças autoimunes reumáticas, particularmente no lúpus eritematoso sistêmico (LES) e na artrite reumatoide (AR). Estudos mostram níveis elevados de leptina e de adiponectina no LES, porém a correlação com a atividade da doença ainda é discutida. Na AR, os estudos também mostram aumento dos níveis de leptina e de adiponectina, observando-se correlação com a atividade da doença e a erosão articular; os resultados, porém, são conflitantes. Esta revisão descreve os papéis da leptina e da adiponectina no sistema imune e suas atuações no LES e na AR.
In recent years, mediators synthesized in the adipose tissue, the so-called adipokines, have been described. They have a hormonal action, regulating appetite and glucose metabolism, but also act as cytokines with effects on the immune system, including effects on autoimmunity. The most important adipokines are leptin, adiponectin, resistin and visfatin, and some of them have been assessed in autoimmune rheumatic diseases, especially systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Studies have shown high levels of leptin and adiponectin in SLE, but correlation with disease activity is questionable. In RA, studies have also reported increased levels of leptin and adiponectin, and correlation with disease activity and joint erosion, but the results are confl icting. This review describes the role of leptin and adiponectin on the immune system, as well as on SLE and RA.
Asunto(s)
Humanos , Adiponectina/inmunología , Artritis Reumatoide/inmunología , Leptina/inmunología , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
In recent years, mediators synthesized in the adipose tissue, the so-called adipokines, have been described. They have a hormonal action, regulating appetite and glucose metabolism, but also act as cytokines with effects on the immune system, including effects on autoimmunity. The most important adipokines are leptin, adiponectin, resistin and visfatin, and some of them have been assessed in autoimmune rheumatic diseases, especially systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Studies have shown high levels of leptin and adiponectin in SLE, but correlation with disease activity is questionable. In RA, studies have also reported increased levels of leptin and adiponectin, and correlation with disease activity and joint erosion, but the results are conflicting. This review describes the role of leptin and adiponectin on the immune system, as well as on SLE and RA.