Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions

Abstract

M1 macrophages release pro-inflammatory factors during inflammation. They transition to an M2 phenotype and release anti-inflammatory factors to resolve inflammation. An imbalance in the transition from M1 to M2 phenotype in macrophages contributes to the development of persistent inflammation. CD163, a member of the scavenger receptor cysteine-rich family, is an M2 macrophage marker. The functional role of CD163 during the resolution of inflammation is not completely known. We postulate that CD163 contributes to the transition from M1 to M2 phenotype in macrophages. We induced CD163 gene in THP-1 and primary human macrophages using polyethylenimine nanoparticles grafted with a mannose ligand (Man-PEI). This nanoparticle specifically targets cells of monocytic origin via mannose receptors. Cells were challenged with a single or a double stimulation of lipopolysaccharide (LPS). A CD163 or empty plasmid was complexed with Man-PEI nanoparticles for cell transfections. Quantitative RT-PCR, immunocytochemistry, and ELISAs were used for molecular assessments. CD163-overexpressing macrophages displayed reduced levels of tumor necrosis factor-alpha (TNF)-α and monocytes chemoattractant protein (MCP)-1 after a single stimulation with LPS. Following a double stimulation paradigm, CD163-overexpressing macrophages showed an increase of interleukin (IL)-10 and IL-1ra, and a reduction of MCP-1. This anti-inflammatory phenotype was partially blocked by an anti-CD163 antibody (effects on IL-10 and IL-1ra). A decrease in the release of TNF-α, IL-1β, and IL-6 was observed in CD163-overexpressing human primary macrophages. The release of IL-6 was blocked by an anti-CD163 antibody in the CD163-overexpressing group. Our data show that the induction of the CD163 gene in human macrophages under inflammatory conditions produces changes in cytokine secretion in favor of an anti-inflammatory phenotype. Targeting macrophages to induce CD163 using cell-directed nanotechnology is an attractive and practical approach for inflammatory conditions that could lead to persistent pain, i.e. major surgeries, burns, rheumatoid arthritis, etc.

Dysfunctional network and mutation genes of hypertrophic cardiomyopathy

“…Macrophages participate in this process by maintaining the in ammatory and brogenic environment (41). CD163 promotes the transformation of macrophages from M1 to M2 phenotype and releases antiin ammatory factors to solve in ammation (42). In our analysis, CD163 was down regulated in HCM, which may be a key factor in the persistent in ammatory environment of HCM.…”

Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerance

“…The present results establish that a tolerogenic vaccine able to mitigate EAE in inbred SPF mice through MOG-targeting to peripheral DC and induction of FOXP3+ suppressor Tregs (Idoyaga et al , 2013; Ring et al , 2013) also applies to outbred adult primates with a trained immune system. In mice, tolerogenic priming relied on the ability of particular DC subsets to produce TGF β (Idoyaga et al , 2013; Ring et al , 2013; Yamazaki et al , 2008), a cytokine also produced by CD163+ M2 macrophages (Zaba et al , 2007; Alvarado-Vazquez et al , 2017). These CD163+ macaque’s skin macrophage have migratory properties as they are also retrieved in lymph nodes (Adam et al , 2015).…”

α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction

“…23,24 Interestingly, CD163overexpressing macrophages inhibit LPS-induced inflammation in vitro. 25 Furuhashi et al. also found that CD163-expressing macrophages are associated with IL-10 production as an anti-inflammatory cytokine in anti-GBM glomerulonephritis rat.…”