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

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-? and the production of pro- (TNF-?, IL-1? 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-?, 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.

SUBMITTER: Bondue B

PROVIDER: S-EPMC3386906 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Bondue Benjamin B De Henau Olivier O Luangsay Souphalone S Devosse Thalie T de Nadaï Patricia P Springael Jean-Yves JY Parmentier Marc M Vosters Olivier O

PloS one 20120629 6

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-infla ...[more]

PMID: 22768214

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Project description:BackgroundChronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels of pro-inflammatory factors in PD brain tissues. The pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease. This is the first report on the co-aggregation of ?-synuclein (?-syn) and S100A9 both in vitro and ex vivo in PD brain.MethodsSingle and sequential immunohistochemistry, immunofluorescence, scanning electron and atomic force (AFM) microscopies were used to analyze the ex vivo PD brain tissues for S100A9 and ?-syn location and aggregation. In vitro studies revealing S100A9 and ?-syn interaction and co-aggregation were conducted by NMR, circular dichroism, Thioflavin-T fluorescence, AFM, and surface plasmon resonance methods.ResultsCo-localized and co-aggregated S100A9 and ?-syn were found in 20% Lewy bodies and 77% neuronal cells in the substantia nigra; both proteins were also observed in Lewy bodies in PD frontal lobe (Braak stages 4-6). Lewy bodies were characterized by ca. 10-23 ?m outer diameter, with S100A9 and ?-syn being co-localized in the same lamellar structures. S100A9 was also detected in neurons and blood vessels of the aged patients without PD, but in much lesser extent. In vitro S100A9 and ?-syn were shown to interact with each other via the ?-syn C-terminus with an apparent dissociation constant of ca. 5 ?M. Their co-aggregation occurred significantly faster and led to formation of larger amyloid aggregates than the self-assembly of individual proteins. S100A9 amyloid oligomers were more toxic than those of ?-syn, while co-aggregation of both proteins mitigated the cytotoxicity of S100A9 oligomers.ConclusionsWe suggest that sustained neuroinflammation promoting the spread of amyloidogenic S100A9 in the brain tissues may trigger the amyloid cascade involving ?-syn and S100A9 and leading to PD, similar to the effect of S100A9 and A? co-aggregation in Alzheimer's disease. The finding of S100A9 involvement in PD may open a new avenue for therapeutic interventions targeting S100A9 and preventing its amyloid self-assembly in affected brain tissues.

Dataset Information

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

Publications

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

Similar Datasets

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