Different effects of adiponectin isoforms in human monocytic cells.
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)-kappaB kinase beta, leading to a diminished nuclear translocation of NF-kappaB 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.
Neumeier
Markus
M
Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany.
Weigert
Johanna
J
Schäffler
Andreas
A
Wehrwein
Gabriele
G
Müller-Ladner
Ulf
U
Schölmerich
Jürgen
J
Wrede
Christian
C
Buechler
Christa
C
D055372:AMP-Activated Protein Kinases; D052242:Adiponectin / Q000096:biosynthesis / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000096:biosynthesis / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051116:Receptors, Scavenger / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology
D052242:Adiponectin; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases