Chemokine-like receptor 1 expression by macrophages in vivo: Regulation by TGF-β and TLR ligands

Zabel, Brian A.; Ohyama, Takao; Zúñiga, Luis A.; Kim, Jiyun; Johnston, Brent; Allen, Samantha J.; Guido, David; Handel, Tracy M.; Butcher, Eugene C.

doi:10.1016/j.exphem.2006.03.011

Cited by 127 publications

(108 citation statements)

References 29 publications

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“…This paradox can be reconciled because these cell types differ in their distinctive physiological functions. ChemR23 expression was downregulated by cardiovascular risk factors, which is consistent with other reports, that showed ChemR23 is downregulated by interleukin-2 or interleukin-15 in NK cells and by proinflammatory cytokines and Toll-like receptor ligands in macrophages [9,22] . The downregulation of ChemR23 expression was correlated with the inhibition of cell migration in response to chemerin in NK cells, which may indicate that the receptor function of ChemR23 is decreased along with its downregulation [9] .…”

Section: Discussionsupporting

confidence: 82%

Chemerin/ChemR23 signaling axis is involved in the endothelial protection by KATP channel opener iptakalim

Zhao

Wang

2011

Acta Pharmacol Sin

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Aim: To elucidate the modulation of the chemerin/ChemR23 axis by iptakalim-induced opening of K ATP channels and to determine the role of the chemerin/ChemR23 axis in the iptakalim-mediated endothelial protection. Methods: Cultured rat aortic endothelial cells (RAECs) were used. Chemerin secretion and ChemR23 protein expression were investigated using Western blot analysis. The gene expression level of ChemR23 was examined with RT-PCR. In addition, the release of nitric oxide (NO) was measured with a nitric oxide assay. Results: Homocysteine, uric acid, high glucose, or oxidized low-density lipoprotein (ox-LDL) down-regulated the chemerin secretion and ChemR23 gene/protein expression in RAECs as a function of concentration and time, which was reversed by pretreatment with iptakalim (1-10 μmol/L). Moreover, these effects of iptakalim were abolished in the presence of the K ATP channel antagonist glibenclamide (1 μmol/L). Both iptakalim and recombinant chemerin restored the impaired NO production in RAECs induced by uric acid, and the effects were abolished by anti-ChemR23 antibodies. Conclusion: Iptakalim via opening K ATP channels enhanced the endothelial chemerin/ChemR23 axis and NO production, thus improving endothelial function.

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Section: Discussionsupporting

confidence: 82%

Chemerin/ChemR23 signaling axis is involved in the endothelial protection by KATP channel opener iptakalim

Zhao

Wang

2011

Acta Pharmacol Sin

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“…The regulation of ChemR23 expression was previously studied in mouse macrophages, where ChemR23 was downregulated by inflammatory stimuli such as TLR ligands (LPS, CpG) and inflammatory cytokines, and upregulated by TGF-b (18,38). The authors of these studies concluded that ChemR23 has a role in naive and anti-inflammatory macrophages only.…”

Section: Discussionmentioning

confidence: 95%

ChemR23, the Receptor for Chemerin and Resolvin E1, Is Expressed and Functional on M1 but Not on M2 Macrophages

Herová

Schmid

Gemperle

et al. 2015

The Journal of Immunology

141

100

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ChemR23 is a G protein–coupled receptor that is triggered by two ligands, the peptide chemerin and the eicosapentaenoic acid–derived lipid mediator resolvin E1 (RvE1). Chemerin acts as a chemoattractant for monocytes and macrophages, whereas RvE1 promotes resolution of inflammation-inducing macrophage phagocytosis of apoptotic neutrophils. Although ChemR23-mediated signaling plays a role in mononuclear cell migration to inflamed tissue, as well as in the resolution of inflammation, its regulation in different polarization states of macrophages is largely unknown. We analyzed the expression and function of ChemR23 in monocytes and differently activated human primary macrophages. Using 5′ RACE, we identified three transcription start sites and several splice variants of ChemR23 in both monocytes and macrophages. Although the promoters P1 and P3 are used equally in unpolarized macrophages, stimulation with LPS or IFN-γ leads to increased transcription from P3 in inflammatory M1 macrophages. Such ChemR23-expressing M1 macrophages are chemotactic to chemerin, whereas M2 macrophages not expressing ChemR23 surface receptor are not. Repolarization of ChemR23-expressing M1 macrophages with 10 nM RvE1 increases IL-10 transcription and phagocytosis of microbial particles, leading to a resolution-type macrophage distinct from the M2 phenotype. These results show that ChemR23 is tightly regulated in response to inflammatory and anti-inflammatory stimuli. The restricted expression of ChemR23 in naive and M1 macrophages supports the role of ChemR23 in the attraction of macrophages to inflamed tissue by chemerin and in the initiation of resolution of inflammation through RvE1-mediated repolarization of human M1 macrophages toward resolution-type macrophages.

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“…Studies on the expression of ChemR23 on murine pDCs have generated conflicting results (9,37). Furthermore, in addition to ChemR23, CXCR4 has been shown to direct the migration of pDCs (38).…”

Section: Dcs In Chemr23mentioning

confidence: 99%

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

Demoor

Bracke

Dupont

et al. 2011

The Journal of Immunology

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Chronic obstructive pulmonary disease is mainly triggered by cigarette smoke (CS) and progresses even after smoking cessation. CS induces an exaggerated influx of inflammatory cells to the bronchoalveolar space and lung parenchyma, likely resulting from a complex interplay between chemoattractants and their respective receptors. In a murine CS model of chronic obstructive pulmonary disease, we studied the importance of chemokine-like receptor ChemR23 for the induction and resolution of inflammation in CS-exposed lungs. Subacute and chronic CS exposure increased protein levels of the ChemR23 ligand and chemoattractant, chemerin, in bronchoalveolar lavage (BAL) fluid of wild-type (WT) mice. Moreover, the proinflammatory chemokines CXCL1, CCL2, and CCL20 were increased in the airways of CS-exposed WT mice, accompanied by a massive accumulation of inflammatory neutrophils and monocytes, CD11bhiCD103− and CD11bloCD103+ dendritic cells (DCs), and CD4+ and CD8+ T cells. The lung parenchyma of WT mice was infiltrated with inflammatory neutrophils, CD11bhiCD103− DCs, and activated CD4+ T cells after CS exposure. CS-induced inflammation was severely attenuated in BAL fluid and lungs of ChemR23 knockout mice with regard to the induction of inflammatory chemokines and the recruitment of inflammatory cells. Neutrophils and CD8+ T cells persisted in the airways of WT mice, as did the airway-derived conventional DCs in the mediastinal lymph nodes, for at least 14 d after smoking cessation. In the BAL fluid of CS-exposed ChemR23 knockout mice, there was a remarkable delayed accumulation of T cells 14 d after the final exposure. Our data support a role for ChemR23 in directing innate and adaptive immune cells to CS-exposed lungs.

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Chemokine-like receptor 1 expression by macrophages in vivo: Regulation by TGF-β and TLR ligands

Cited by 127 publications

References 29 publications

Chemerin/ChemR23 signaling axis is involved in the endothelial protection by KATP channel opener iptakalim

Chemerin/ChemR23 signaling axis is involved in the endothelial protection by KATP channel opener iptakalim

ChemR23, the Receptor for Chemerin and Resolvin E1, Is Expressed and Functional on M1 but Not on M2 Macrophages

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

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