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Updated: Sep 12, 2025
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Melanocortin Receptor-Mediated Anti-Inflammatory Effect of Acthar® Gel in Human Myeloid Cells
1Mallinckrodt Pharmaceuticals, Bridgewater, New Jersey, USA, kyle.hayes@mnk.com.
Abstract:
Introduction: Acthar® Gel, a complex mixture of porcine adrenocorticotropic hormone analogs that activates all 5 melanocortin receptor (MCR) subtypes, is an approved noncorticosteroid treatment for multiple sclerosis (MS) exacerbations.
Methods:
MCR expression and anti-inflammatory effects of Acthar Gel in human monocyte-derived macrophages (MDMs) and human brain-derived microglia were investigated following lipopolysaccharide stimulation in vitro.
Results:
MC1R was expressed at substantially higher levels than the other MCR subtypes in human MDMs and was the only MCR gene detected in human adult microglia. As shown by microarray gene expression analysis, polarization of MDMs to a pro-inflammatory phenotype increased the expression and secretion of interleukin-6, tumor necrosis factor α, and CXC motif chemokine ligand 10, which were inhibited in a dose-dependent manner with Acthar Gel treatment.
Conclusions:
These results are consistent with previous insights that Acthar Gel has an immunomodulatory mechanism distinct from glucocorticoids alone and suggest that Acthar Gel can improve clinical outcomes in MS and other inflammation-mediated central nervous system disorders by inhibiting multiple pro-inflammatory cytokine signaling pathways.
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