Synergy between adiponectin and interleukin-1beta on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1beta regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1beta, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1beta to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1beta each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1beta did not synergistically support the degradation of IkappaB-alpha or the nuclear translocation of NF-kappaB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-kappaB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1beta may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.

Estudo das adipocitoquinas (leptina e adiponectina) do cordão umbilical: relação com o crescimento perinatal / Study of adipokines (leptin and adiponectin) from the umbilical cord: relationship with perinatal growth

O tecido adiposo secreta uma série de proteínas com importância metabólica, como a leptina e adiponectina. A leptina é uma proteína de 16-kDa, sintetizada pelos adipócitos e também pela placenta. Em camundongos, a leptina apresenta papel importante na função neuroendócrina, na fertilidade, na obesidade e diabetes. Nos seres humanos, a leptina está correlacionada com a massa gorda corpórea e balanço energético, além de apresentar variações conforme o sexo e o desenvolvimento puberal. Estudos recentes apontam que a leptina está diretamente relacionada com o processo de regulação de ganho de peso perinatal. No entanto, não existem estudos no Brasil sobre a variabilidade da leptina conforme o crescimento perinatal. A adiponectina é uma proteína com 244 aminoácidos que está paradoxalmente reduzida em pacientes obesos e está inversamente relacionada com os níveis de leptina. Estudos demonstram que a adiponectina possui propriedades anti-inflamatórias e anti-aterogênicas. Há carências de estudos que avaliem suas concentrações em recém-nascidos. Os objetivos deste estudo mediante a apresentação de quatro artigos foram: avaliar a influência da leptina e da adiponectina do sangue do cordão umbilical no crescimento perinatal, por meio da comparação dos seus valores conforme sexo do recém-nascido, idade gestacional, índice ponderal, peso e comprimento de nascimento; verificar se existe corrrelação entre leptina e hormônios sexuais (estradiol e testosterona do cordão umbilical) e determinar se o tabagismo matemo altera os níveis de leptina e adiponectina do cordão umbilical. Em todos os artigos realizou-se pesquisa transversal, em recém-nascidos adequados para idade gestacional, sendo dosados os níveis das adipocitoquinas do cordão umbilical. A análise dos resultados do primeiro artigo ..J .I demonstrou que a leptina do cordão umbilical correlaciona-se positivamente com a idade gestacional, peso, comprimento e índice ponderal do recém-nascimento...

The adipose tissue secretes a variety of honnones with metabolical importance,. such as leptin and adiponectin. Leptin is 16-kDa protein, produced by adipocytes and placenta. In rats, leptin plays an important role in the neuroendocrine function, fertility, obesity and diabetes. In the human beings, leptin is correlated with body fat mass and energy balance, besides this hormone presents variations according to gender and puberal development. Recent studies point that leptin is directly related with the regulation process of neonatal weight gain. However, there are no studies in Brazil about leptin variability in newborns. Adiponectin is a 244-amino acid adipocyte-derived protein that is paradoxically reduced in obese patients and inversely related to leptin concentrations. Some reports demonstrated that adiponectin is a adipokine with anti-inflammatory and antiatherogenic properties. There are very few reports about adiponectin concentrations in newborns. The aim of this . I I study by the presentation of four articles were: to evaluate the influence of cord blood leptin and adiponectin in the neonatal growth, through the comparison of their values according to gender, gestational age, birth weight, length and newborns ponderal index; to verify if there is a correlation between leptin and sexual hormones (estradiol and testosterone in the umbilical cord blood) and to detennine whether maternal smoking modifies leptin and adiponectin levels in the umbilical cord blood. Cross-sectional research had been done in all articles, the subjects selected were all appropriate for gestational age newborns and also the adipokines levels had been dosed in the umbilical cord blood. The analysis of the results on the first article demonstrated that the levels of leptin were correlated positively with gestational age, weight, length and newborns' ponderal index, suggesting leptin participation in the process of neonatal growth. Moreover...