Regulation of CD163 mRNA and soluble CD163 protein in human adipose tissue in vitro

Abstract

CD163-positive macrophages are highly expressed in the human adipose tissue (AT) particularly from obese individuals. However, little is known about the regulation of CD163 mRNA and the protein level of sCD163 in human AT. We aimed to examine the regulation of CD163 and sCD163 in AT. Human s.c. AT samples (nZ5) were stimulated with dexamethasone (DEX; 200 nmol/l), lipopolysaccharide (LPS; 100 ng/ml), or DEXCLPS for various time periods up to 24 h. Gene expressions of CD163, ADAM17, IL10, and TNFA (TNF) were measured by RT-PCR. Protein levels of sCD163, IL10, and TNFa (TNF) were measured by ELISA. Furthermore, AT was separated into stromal and adipocyte fraction. We found that CD163 mRNA was strongly expressed in the stromal vascular fraction but hardly detectable in the isolated adipocytes. Incubating whole AT with DEX significantly up-regulated CD163 (P!0.001), whereas incubation with LPS had no effects on CD163 (PO0.05). By contrast, the protein level of sCD163 was not affected by DEX (PO0.05), but LPS significantly increased the level of sCD163 and TNFa (P!0.05). This might be due to the concomitant LPS stimulation of ADAM17, which is known to mediate shedding of the extracellular domains of sCD163 and TNFa. Finally, DEX significantly reduced the LPS-induced TNFa release to the incubation medium but had no effects on sCD163. We conclude that the expression of CD163 and the release of sCD163 are differentially regulated in human AT. Moreover, similar to studies on differentiated blood monocytes, TNFa and sCD163 are concomitantly released in human AT by LPS, which also up-regulate ADAM17.

Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s

“…Microbial translocation may also play a role in the association seen between sCD163 and insulin resistance. Markers of microbial translocation have been associated with insulin resistance [ 37 ] and are known to stimulate the release of sCD163 [ 38 ].…”

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

“…This is in keeping with a number of studies that have identified associations between sCD163 and cardiovascular inflammation and atherosclerotic plaque formation in the setting of HIV infection [ 14 , 23 – 25 ] as well as in the general population [ 23 , 26 , 27 ]. This association appears to be underpinned by the role of activated monocyte-derived macrophages within atherosclerotic vessels [ 28 ] as well as in adipose tissue [ 29 , 30 ] in producing sCD163. This pathway involves tumor necrosis factor-alpha (TNF-α) and ADAM-17 [ 30 , 31 ], thus providing a link between inflammation and atherosclerotic risk factors including oxidised lipids that may be particularly relevant in HIV infection [ 32 , 33 ] but are rarely measured in routine care.…”

“…This association appears to be underpinned by the role of activated monocyte-derived macrophages within atherosclerotic vessels [ 28 ] as well as in adipose tissue [ 29 , 30 ] in producing sCD163. This pathway involves tumor necrosis factor-alpha (TNF-α) and ADAM-17 [ 30 , 31 ], thus providing a link between inflammation and atherosclerotic risk factors including oxidised lipids that may be particularly relevant in HIV infection [ 32 , 33 ] but are rarely measured in routine care.…”

Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country

“…We have previously reported that elevated circulating IL-6 levels are associated with worsened lung function [18], increased exacerbations of airway disease [33], and neutrophilic asthma [34]. In adipose tissue, CD163 gene expression reflects the level of anti-inflammatory (M2) macrophage infiltration [35]. Our finding of increased CD163 gene expression in adipose tissue from Greenland dwelling Inuit is consistent with a less inflammatory state, which is corroborated by finding less IL-6 and IL-1b in Greenland dwelling Inuit adipose tissue biopsies.…”