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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents

ID: 682126.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
The role of HCA2 (GPR109A) in regulating macrophage function
Authors:Zandi-Nejad, K.; Takakura, A.; Jurewicz, M.; Chandraker, A. K.; Offermanns, S.; Mount, D.; Abdi, R.
Date of Publication (YYYY-MM-DD):2013-11
Journal Abbrev.:FASEB J
Issue / Number:11
Start Page:4366
End Page:4374
Audience:Not Specified
Abstract / Description:We investigated the novel role of HCA2 (GPR109A) and its ligand nicotinic acid in regulating macrophage function. Hca2 expression in the RAW264.7 murine macrophage cell line is strongly induced by LPS treatment and correlates with the expression of TNF-alpha. Treatment with 300 muM nicotinic acid (reported EC50 3 muM, peak plasma concentration 50-300 muM), significantly inhibited TNF-alpha, IL-6, IL-12p40, and IL-1beta production (P<0.05) in LPS (1 ng/ml)-stimulated wild-type murine bone marrow-derived macrophages (BMMs) but failed to do so in Hca2(-/-) BMMs. Treatment with nicotinic acid reduced nuclear factor kappaB (NF-kappaB) activation levels by 43% (P<0.03) in wild-type BMMs 6 h after LPS stimulation but not in Hca2(-/-) BMMs. Nicotinic acid significantly inhibited wild-type BMM chemotaxis (P<0.001), but had no effect on the chemotaxis of Hca2(-/-) BMMs. A significant increase in low-density lipoprotein uptake by both wild-type (P<0.006) and Hca2(-/-) BMMs (P<0.03) in response to LPS was observed, which was significantly suppressed by nicotinic acid in wild-type BMMs (P<0.04) but not in Hca2(-/-) BMMs. Our results suggest that the nicotinic acid-HCA2 axis is a novel negative regulator of macrophage activation.
Free Keywords:Animals; Biological Transport, Active/drug effects; Cell Line, Tumor; Chemotaxis/drug effects; Interleukins/genetics/metabolism; Lipopolysaccharides/pharmacology; Lipoproteins, LDL/metabolism; *Macrophage Activation; Macrophages/immunology/*metabolism; Mice; NF-kappa B/metabolism; Niacin/pharmacology; Receptors, G-Protein-Coupled/agonists/genetics/*metabolism; Receptors, Nicotinic/genetics/*metabolism; Tumor Necrosis Factor-alpha/pharmacology
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1530-6860 (Electronic) 0892-6638 (Linking) %R 10.1096/fj.12-223933
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