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Stéphane Brézillon

Bio: Stéphane Brézillon is an academic researcher from University of Reims Champagne-Ardenne. The author has contributed to research in topics: Lumican & Receptor. The author has an hindex of 24, co-authored 53 publications receiving 4804 citations.


Papers
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Journal ArticleDOI
TL;DR: Stimulation of oxytocin secretion after kisspeptin administration to rats confirmed this hypothesis that human GPR54 was highly expressed in placenta, pituitary, pancreas, and spinal cord, suggesting a role in the regulation of endocrine function.

1,431 citations

Journal ArticleDOI
TL;DR: The pharmacology of GPR43 matches indeed the effects of SCFAs on neutrophils, in terms of intracellular Ca2+ release and chemotaxis, and might constitute a target allowing us to modulate immune responses in these pathological situations.

1,316 citations

Journal ArticleDOI
TL;DR: Chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs, and was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner.
Abstract: Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.

833 citations

Journal ArticleDOI
TL;DR: In CHO-K1 cells expressing the P2Y13 receptor, ADP and 2MeSADP had a biphasic effect on the forskolin-stimulated accumulation of cAMP: inhibition at nanomolar concentrations and potentiation at micromolar levels.

324 citations

Journal ArticleDOI
TL;DR: The primary goal of this comprehensive review is to summarize major achievements and paradigm-shifting discoveries made on the PG/GAG chemistry-biology axis, focusing on structural variability, structure-function relationships, metabolic, molecular, and epigenetic mechanisms underlying their synthesis.
Abstract: The extracellular matrix (ECM) constitutes a highly dynamic three-dimensional structural network comprised of macromolecules, such as proteoglycans/glycosaminoglycans (PGs/GAGs), collagens, laminins, fibronectin, elastin, other glycoproteins and proteinases In recent years, the field of PGs has expanded rapidly Due to their high structural complexity and heterogeneity, PGs mediate several homeostatic and pathological processes PGs consist of a protein core and one or more covalently attached GAG chains, which provide the protein cores with the ability to interact with several proteins The GAG building blocks of PGs significantly influence the chemical and functional properties of PGs The primary goal of this comprehensive review is to summarize major achievements and paradigm-shifting discoveries made on the PG/GAG chemistry-biology axis, focusing on structural variability, structure-function relationships, metabolic, molecular, and epigenetic mechanisms underlying their synthesis Recent insights related to exosome biogenesis, degradation, and cell signaling, their status as diagnostic tools and potential pharmacological targets in diseases as well as current applications in nanotechnology and biotechnology are addressed Moreover, issues related to docking studies, molecular modeling, GAG/PG interaction networks, and their integration are discussed

226 citations


Cited by
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Journal ArticleDOI
02 Aug 2013-Science
TL;DR: This study determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice, revealing that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
Abstract: Regulatory T cells (T regs ) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate T reg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic T regs . We determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic T reg pool and protect against colitis in a Ffar2 -dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.

3,733 citations

Journal ArticleDOI
02 Jun 2016-Cell
TL;DR: Data is reviewed supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs), which affect various physiological processes and may contribute to health and disease.

3,363 citations

Journal ArticleDOI
TL;DR: This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism.

3,040 citations

Journal ArticleDOI
TL;DR: The present review focuses on the organisation of descending pathways and their pathophysiological significance, the role of individual transmitters and specific receptor types in the modulation and expression of mechanisms of descending inhibition and facilitation and the advantages and limitations of established and innovative analgesic strategies which act by manipulation of descending controls.

2,565 citations

Journal ArticleDOI
29 Oct 2009-Nature
TL;DR: It is shown that SCFA–GPR43 interactions profoundly affect inflammatory responses, and GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
Abstract: The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases. One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and other colitic diseases is a change in 'healthy' microbiota such as Bifidobacterium and Bacteriodes, and a concurrent reduction in SCFAs. Moreover, increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically beneficial in the treatment of colitis. SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2), and here we show that SCFA-GPR43 interactions profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for the normal resolution of certain inflammatory responses, because GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving inflammation in models of colitis, arthritis and asthma. This seemed to relate to increased production of inflammatory mediators by Gpr43(-/-) immune cells, and increased immune cell recruitment. Germ-free mice, which are devoid of bacteria and express little or no SCFAs, showed a similar dysregulation of certain inflammatory responses. GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.

2,515 citations