Induction of chemokine expression by adiponectin in vitro is isoform dependent

Adiponectin is reported to have both proinflammatory and anti-inflammatory effects. Because adiponectin circulates in isoforms of various sizes and some responses to adiponectin are isoform dependent, it was postulated that the proinflammatory effects of adiponectin may be isoform specific. To test this theory, peripheral blood mononuclear cells (PBMCs), microvascular endothelial cells (MVECs), and human glomerular mesangial cells (HMCs) were treated with high-molecular-weight (HMW) or low-molecular-weight (LMW) recombinant human adiponectin, and chemokine production was measured. The PBMCs were isolated from healthy volunteers by density gradient centrifugation of ethylenediaminetetraacetic acid (EDTA) anticoagulated whole blood through endotoxin-free Ficoll (General Electric Healthcare Bio-Sciences, Uppsala, Sweden). The MVECs were of dermal origin, and the HMCs were isolated from kidneys not suitable for transplantation. Overnight (16 h) incubation with HMW adiponectin (0.01-1 microg/mL for PBMCs; 5-20 microg/mL for MVECs and HMCs) induced a dose-dependent increase in production of monocyte chemoattractant protein-1 and interleukin-8 by PBMCs and MVECs, but it had no effect on HMC chemokine production (n=3-5). LMW adiponectin at the same concentrations did not induce chemokine production in any of the cell types tested, and it did not block cytokine-induced chemokine production by PBMCs or MVECs (n=3-5). These in vitro data suggested that the HMW adiponectin isoform is proinflammatory. To examine the possibility of a relationship between HMW adiponectin and inflammation in vivo, the urine of patients with systemic lupus erythematosus (SLE) and kidney involvement, which was shown previously to contain immunoreactive adiponectin, was examined for the presence of specific adiponectin isoforms by nondenaturing gel electrophoresis. HMW adiponectin was found in the urine of patients with active lupus nephritis. Therefore, HMW adiponectin may contribute to the renal inflammation of SLE.