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Published online before print January 24, 2006

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(Journal of Leukocyte Biology. 2006;79:803-808.)
© 2006 by Society for Leukocyte Biology

Different effects of adiponectin isoforms in human monocytic cells

Department of Internal Medicine I, University of Regensburg, Germany

¹Correspondence: Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany. E-mail: christa.buechler{at}klinik.uni-regensburg.de

Adiponectin (APM) is an adipocyte-derived adipokine with immunosuppressive, antidiabetic, and antiatherosclerotic properties. Low molecular weight (LMW)- and higher molecular weight (HMW)-APM circulate in the serum and activate different signaling pathways. We were interested to see whether LMW-APM exerts different effects on monocytic cells compared with the HMW isoform. Therefore, the effects of recombinant LMW-APM produced in insect cells and the APM from higher eukaryotic cells containing HMW forms on monocytic cells were investigated with respect to apoptosis and inflammation. LMW- and HMW-APM induce apoptosis in nondifferentiated THP-1 cells, reduce macrophage scavenger receptor (MSR) A mRNA expression, and stimulate phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). However, HMW-APM induces the secretion of interleukin (IL)-6 in human monocytes and THP-1 cells but does not suppress lipopolysaccharide (LPS)-induced IL-6 secretion. In contrast, LMW-APM reduces LPS-mediated IL-6 release and furthermore, stimulates IL-10 secretion, most likely by reducing the abundance of inhibitor of nuclear factor (NF)-B kinase ß, leading to a diminished nuclear translocation of NF-B p65. Our data indicate that the different APM isoforms do share common effects on monocytic cells but also induce isoform-specific responses. Although apoptosis, the activation of AMPK, and the reduction of MSR are mediated by all APM isoforms, only LMW-APM displays anti-inflammatory properties.

Key Words: endotoxin • inflammation • adipokine • diabetes

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