ABSTRACT
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.
Subject(s)
Humans , Adiponectin/administration & dosage , Arthritis, Rheumatoid/metabolism , Cells, Cultured , Cyclooxygenase 2/metabolism , Gene Expression Regulation/drug effects , Inflammation/metabolism , Interleukin-1beta/administration & dosage , Interleukin-6/metabolism , Interleukin-8/metabolism , Joints/metabolism , Matrix Metalloproteinases , NF-kappa B/metabolism , Obesity/metabolism , Osteoarthritis , Receptors, Adiponectin/metabolism , Receptors, Interleukin-1/metabolism , Synovial Fluid/cytologyABSTRACT
In this study, data from a pandemic H1N1 outbreak in Korea were analyzed according to time, geography (districts), and age. A total of 252,271 samples collected nationwide were referred to the Greencross Reference Laboratory from June 2009 to February 2010 for H1N1 confirmation testing. Of these samples, 105,300 (41.7%) were H1N1-positive. With time, positivity was highest (57.0%) from October 26 - November 1 (4 weeks after Chuseok). The positive rates among districts show the highest value in Ulsan City (63.1%) and the lowest in Gyeongnam Province (32.8%). The positive rates for ages 0-2, 3-5, 6-11, 12-17, 18-20, 21-30, 31-40, 41-50, 51-60, and > 60 yr were 17.0%, 33.1%, 56.2%, 55.5%, 55.3%, 41.5%, 28.2%, 30.5%, 31.1%, and 16.8%, respectively, indirectly indicating propagation of H1N1 through schools. Pandemic control should involve school-targeted strategies.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Influenza A Virus, H1N1 Subtype , Influenza, Human/epidemiology , Pandemics/prevention & control , Republic of Korea/epidemiology , StudentsABSTRACT
The gradual loss of telomeric DNA can contribute to replicative senescence and thus, having longer telomeric DNA is generally considered to provide a longer lifespan. Maintenance and stabilization of telomeric DNA is assisted by binding of multiple DNA-binding proteins, including those involved in double strand break (DSB) repair. We reasoned that declining DSB repair capacity and increased telomere shortening in aged individuals may be associated with decreased expression of DSB repair proteins capable of telomere binding. Our data presented here show that among the DSB repair proteins tested, only the expression of Ku70 and Mre11 showed statistically significant age-dependent changes in human lymphocytes. Furthermore, we found that expressions of Ku70 and Mre11 are statistically correlated, which indicate that the function of Ku70 and Mre11 may be related. All the other DSB repair proteins tested, Sir2, TRF1 and Ku80, did not show any significant differences upon aging. In line with these data, people who live in the regional community (longevity group), which was found to have statistically longer average life span than the rest area, shows higher level of Ku70 expression than those living in the neighboring control community. Taken together, our data show, for the first time, that Ku70 and Mre11 may represent new biomarkers for aging and further suggest that maintenance of higher expression of Ku70 and Mre11 may be responsible for keeping longer life span observed in the longevity group.