Glucocorticoids Enhance CD163 Expression in Placental Hofbauer Cells

Abstract

Periplacental levels of glucocorticoid (GC) peak at parturition, and synthetic GC is administered to women at risk for preterm delivery. However, little is known concerning cell-type-specific effects of GC in placenta. Hofbauer cells (HBCs) are fetal macrophages that are located adjacent to fetal capillaries in placenta. The goal of the current study was to determine whether GC treatment altered HBC gene expression and function. Western blotting and flow cytometry revealed CD163 and folate receptor-β (FR-β), markers of antiinflammatory M2 macrophages, were specifically expressed by primary cultures of HBCs immunopurified from human term placentas. GC receptor mRNA and protein levels were higher in HBCs compared with placental fibroblasts. Treatment of HBCs with cortisol or dexamethasone (DEX) markedly and specifically enhanced CD163 protein and mRNA levels, whereas expression of FR-β and CD68 were largely unresponsive to GC treatment. DEX treatment also increased hemoglobin uptake by HBCs, evidence of enhanced HBC function. The level of CD163 mRNA, but not FR-β or CD68 mRNA, was stimulated in placental explant cultures by DEX treatment, and increased CD163/FR-β and CD163/CD68 mRNA ratios sensitively reflected the response to GC. Maternal GC administration was associated with increased CD163/FR-β and CD163/CD68 mRNA ratios in placentas from women with spontaneous preterm birth. In conclusion, in vitro studies indicated that GC treatment specifically up-regulated CD163 expression in HBCs and enhanced HBC function. In addition, the observed alterations in patterns of expression of macrophage marker genes associated with maternal GC administration suggest that HBCs are in vivo targets of GC action.

Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta

“…Expression of CD163 has been associated with an anti-inflammatory (M2) macrophage phenotype. 49,50 The putative relationship of CD163 to iron homeostasis and macrophage polarization is summarized in Figure 4. Anti-inflammatory mediators such as IL-10 promote the expression of CD163 while pro-inflammatory mediators such as IFN-γ and TNF-α have been shown to decrease its expression.…”

“…Expression of CD163 has been associated with an anti-inflammatory (M2) macrophage phenotype. 49,50 The putative relationship of CD163 to iron homeostasis and macrophage polarization is summarized in Figure 4.…”

The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

“…While glucocorticoids are potent inducers of increments in CD163 expression, this does not necessarily increase levels of sCD163 in plasma, but when accompanied by an inflammatory stimulus it gives rise to increased cleavage activity of a disintegrin and metalloproteinase 17 known as ADAM17 and TNFα converting enzyme (TACE), resulting in increased shedding of sCD163 from the cell surface of the glucocorticoid-activated machrophages (50). Neither E 2 nor testosterone gave rise to increased expression of CD163 in an in vitro experiment, pointing out this intangible association between CD163 expression and the soluble form of CD163 (23).…”

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

“…Hofbauer cells, which display homeostatic properties within the M2 range and may have an important phagocytic function during placental formation (Bulmer and Johnson, 1984;Bockle et al, 2008;Tang et al, 2013).…”