Different effects of adiponectin isoforms in human monocytic cells
Different effects of adiponectin isoforms in human monocytic cells
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DOI：
10.1189/jlb.0905521
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发表时间：
2006-04-01
影响因子：
5.5
通讯作者：
Buechler, Christa
中科院分区：
文献类型：
--
作者：
Neumeier, Markus;Weigert, Johanna;Buechler, Christa
脂联素（APM）是一种脂肪细胞源性脂肪因子，具有免疫抑制、抗糖尿病和抗动脉粥样硬化的特性。低分子量（LMW）和高分子量（HMW）-APM在血清中循环并激活不同的信号通路。我们感兴趣的是，看看是否LMW-APM发挥不同的作用，单核细胞与HMW异构体相比。因此，研究了昆虫细胞中产生的重组LMW-APM和来自含有高分子量形式的高等真核细胞的APM对单核细胞凋亡和炎症的影响。LMW-和HMW-APM诱导未分化THP-1细胞凋亡，降低巨噬细胞清道夫受体（MSR）A mRNA表达，并刺激腺苷磷酸活化蛋白激酶（AMPK）的磷酸化。然而，HMW-APM诱导人单核细胞和THP-1细胞分泌白细胞介素（IL）-6，但不抑制脂多糖（LPS）诱导的IL-6分泌。相比之下，LMW-APM减少LPS介导的IL-6释放，此外，刺激IL-10分泌，最有可能是通过减少核因子（NF）-κ B激酶β抑制剂的丰度，导致NF-κ B p65的核转位减少。我们的数据表明，不同的APM亚型。s对单核细胞ceR具有共同的作用，但也诱导同种型特异性反应。尽管细胞凋亡、AMPK的激活和MSR的减少由所有APM同种型介导，但只有LMW-APM显示抗炎特性。
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 non-differentiated THP-1 cells, reduce macrophage scavenger receptor (MSR) A mRNA expression, and stimulate phosphorylation of adenosine nionophosphate-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)-kappa B kinase beta, leading to a diminished nuclear translocation of NF-kappa B p65. Our data indicate that the different APM isoform. s do share common effects on monocytic ceRs 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.