Article

The chemerin/ChemR23 system does not affect the pro-inflammatory response of mouse and human macrophages ex vivo.

Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium.
PLoS ONE (Impact Factor: 3.53). 01/2012; 7(6):e40043. DOI: 10.1371/journal.pone.0040043
Source: PubMed

ABSTRACT Macrophages constitute a major component of innate immunity and play an essential role in defense mechanisms against external aggressions and in inflammatory responses. Chemerin, a chemoattractant protein, is generated in inflammatory conditions, and recruits cells expressing the G protein-coupled receptor ChemR23, including macrophages. Chemerin was initially expected to behave as a pro-inflammatory agent. However, recent data described more complex activities that are either pro- or anti-inflammatory, according to the disease model investigated. In the present study, peritoneal macrophages were generated from WT or ChemR23(-/-) mice, stimulated with lipopolyssaccharide in combination or not with IFN-γ and the production of pro- (TNF-α, IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was evaluated using qRT-PCR and ELISA. Human macrophages generated from peripheral blood monocytes were also tested in parallel. Peritoneal macrophages from WT mice, recruited by thioglycolate or polyacrylamide beads, functionally expressed ChemR23, as assessed by flow cytometry, binding and chemotaxis assays. However, chemerin had no effect on the strong upregulation of cytokine release by these cells upon stimulation by LPS or LPS/IFN-γ, whatever the concentration tested. Similar data were obtained with human macrophages. In conclusion, our results rule out the direct anti-inflammatory effect of chemerin on macrophages ex vivo, described previously in the literature, despite the expression of a functional ChemR23 receptor in these cells.

1 Bookmark
 · 
154 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemerin is an immunomodulating factor secreted predominantly by adipose tissue and skin. Processed by a variety of proteases linked to inflammation, it activates the G-protein coupled receptor chemokine-like receptor 1 (CMKLR1) and induces chemotaxis in natural killer cells, macrophages, and immature dendritic cells. Recent developments revealed the role of the nonsignaling chemerin receptor C-C chemokine receptor-like 2 (CCRL2) in inflammation. Besides further research establishing its link to inflammatory skin conditions such as psoriasis, functions in healthy skin have also been reported. Here, the current understanding of chemerin processing, signaling and physiological function has been summarized, focusing on the regulation of its activity, its different receptors and its controversially discussed role in diseases. © 2014 IUBMB Life, 2014.
    International Union of Biochemistry and Molecular Biology Life 01/2014; · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemerin is an adipocyte-secreted protein with autocrine/paracrine roles on adipose development and function as well as endocrine roles in metabolism and immunity. Following prochemerin secretion, protease-mediated generation of chemerin isoforms with a range of biological activities is a key regulatory mechanism controlling local, context-specific chemerin bioactivity. Together, experimental and clinical data indicate that localized and/or circulating chemerin expression and activation are elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. These elevations are positively correlated with deleterious changes in glucose, lipid, and cytokine homeostasis, and may serve as a link between obesity, inflammation and other metabolic disorders. This review highlights the current state of knowledge regarding chemerin expression, processing, biological function and relevance to human disease, particularly with respect to adipose tissue development, inflammation, glucose homeostasis and cardiovascular disease. Furthermore, it discusses study variability, deficiencies in current measurement, and questions concerning chemerin function in disease, with a special emphasis on techniques and tools used to properly assess chemerin biology. An integration of basic and clinical research is key to understanding how chemerin influences disease pathobiology, and whether modulation of chemerin levels and/or activity may serve as a potential method to prevent and treat metabolic diseases.
    Obesity Reviews 12/2012; · 6.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Depending on their anatomical location, different fat depots have a different capacity to produce bioactive peptides, called adipokines. Adipokines produced by periadventitial fat have been implicated in the pathogenesis of vascular disease, including atherosclerosis. Chemerin is an adipokine with an established role in immunity, adipose tissue function and metabolism, acting in autocrine, paracrine and endocrine manners. We investigated the protein expression of chemerin and its receptor, CMKLR1, in human aortas, coronary vessels and the respective periadventitial adipose tissue and correlated their expression with the presence of atherosclerosis. Immunohistochemistry for chemerin and CMKLR1 was performed on human aortic and coronary artery samples including the periadventitial adipose tissue. Aortic and coronary atherosclerotic lesions were assessed using the AHA classification. Chemerin immunopositivity was noticed in both periadventitial fat depots, in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Periadventitial fat and foam cell chemerin immunopositivity was statistically significantly correlated with the severity of atherosclerosis in both locations. CMKLR1 was expressed in vascular smooth muscle cells and foam cells in aortic and coronary vessels with atherosclerotic lesions. CMKLR1 immunostaining in foam cells was statistically significantly correlated with aortic atherosclerosis. Our results lend some support to a presumable role of locally produced chemerin in the progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor. Further research will elucidate the role of chemerin signaling in atherosclerosis.
    BMC Cardiovascular Disorders 04/2014; 14(1):56. · 1.46 Impact Factor

Full-text (2 Sources)

View
117 Downloads
Available from
Jun 6, 2014