VIP in Inflammatory Bowel Disease: State of the Art
The Semel Institute and Department of Psychiatry The David Geffen School of Medicine, University of California, Los Angeles, CA 90095. .
Endocrine, metabolic & immune disorders drug targets
06/2012; 12(4). DOI: 10.2174/187153012803832576
The pathogenesis of inflammatory bowel syndrome (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC) is poorly understood. However, an inflammatory component is a common hallmark. It has been suggested that CD principally involves Th1 and/or Th17 cells, while UC is considered to be more Th2 driven. Because vasoactive intestinal peptide (VIP) has emerged in the last decade as a putative candidate for the treatment of inflammatory diseases with a Th1 component, it may as well serve as a therapeutic target in CD. In addition, experiments using mice deficient in VIP or its receptors have revealed that the endogenously-produced VIP may participate in the regulation of immunity. The aim of the present review is to summarize the quite considerable array of data which suggests that the VIP-receptor system plays a key role in modulating multiple molecular and cellular players involved in IBD.
Available from: Xinyun Qiu
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ABSTRACT: Background and aims: Faecalibacterium prausnitzii (F. prausnitzii) is a common anaerobic bacteria colonized in the human gut and inflammatory bowel disease (IBD) patients are usually lack of F. prausnitzii. The aims of this study were to evaluate the anti-inflammatory and immunomodulatory capacity of F. prausnitzii by comparing it with Bifidobacterium longum (B. longum) in both cellular and animal experiments.
Methods: Human peripheral blood mononuclear cells (PBMCs) and 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colitis rat models were treated with F. prausnitzii, B. longum, F. prausnitzii supernatant or F. prausnitzii medium, respectively. Interleukin (IL)-10, TGF-β1 and IL-12p70 in human PBMCs culture supernatant and rat blood serum were detected. The frequency of CD25+Foxp3+Treg in human PBMCs, rat PBMCs and rat splenocytes were investigated. Besides, the T-bet, GATA-3, ROR-γt and Foxp3 mRNA in human PBMCs, histopathologic characteristics of the intestinal mucosal and weight loss in the rat models were examined.
Results: F. prausnitzii, B. longum and F. prausnitzii supernatant clearly facilitated the induction of IL-10 and TGF-β1, while induced relatively mild production of IL-12p70 in both cellular and animal models. The F. prausnitzii, B. longum and supernatant differed in their capacity to induce T-bet, GATA-3 and ROR-γt mRNA expression in human PBMCs (both bacterial strains inhibited the expression of ROR-γt while supernatant inhibited the T-bet and GATA-3). However, all of them induced the Foxp3 and Treg production and ameliorated the TNBS-induced colitis. In addition, F. prausnitzii supernatant exhibited the supreme anti-inflammatory capacity.
Conclusions: F. prausnitzii and its unidentified metabolites in the supernatant are promising candidates in treating IBD, and further research remains necessary to elucidate the safety, efficacy, optimum and mechanism of this bacterium in the clinical practice.
Journal of Crohn s and Colitis 05/2013; 7(11). DOI:10.1016/j.crohns.2013.04.002 · 6.23 Impact Factor
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ABSTRACT: Crohn's disease and ulcerative colitis are the major inflammatory bowel diseases (IBD) in humans. With its incidence increasing world-wide, it currently affects 4 million people in Europe and in the USA. It is an idiopathic, chronic relapsing intestinal disorder of complex pathogenesis. The etiology of both diseases remains unknown, but recent data suggest that they appear in genetically predisposed individuals, because of an exaggerated mucosal immune response to commensal microbiota present in the gut. There is increasing evidence for an alteration of the immune regulation mechanisms in patients, with mucosal T lymphocytes playing a crucial role in the pathogenic events leading to tissue damage. It is clear that the disease is the result of environmental factors acting on genetically predisposed individuals. In humans, psychological trauma, stress or depression, have been involved as precipitating or relapsing factors of the disease, although this link remains elusive. However, several published works using colitis animal models subjected to stress conditions, have given consistent proof as to the molecular link between emotional stress, increase in epithelial permeability, alteration of the gut microflora composition and activation of pre-sensitized T lymphocytes. Gaining knowledge of the cross talk between components of the brain - gut - immune system axis may be fruitful in the design of future therapeutic approaches, such as the use of vasointestinal peptide (VIP) in this pathology.
Current pharmaceutical design 01/2014; 20(29). DOI:10.2174/1381612820666140130205058 · 3.45 Impact Factor
Available from: Amitabha Chaudhuri
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ABSTRACT: The M1 and M2 states of macrophage polarization are the two extremes of a physiologic/phenotypic continuum that is dynamically influenced by environmental signals. The M1/M2 paradigm is an excellent framework to understand and appreciate some of the diverse functions that macrophages perform. Molecular analysis of mouse and human macrophages indicated that they gain M1 and M2-related functions after encountering specific ligands in the tissue environment. In this perspective, I discuss the function of recepteur d'origine nantais (RON) receptor tyrosine kinase in regulating the M2-like state of macrophage activation Besides decreasing pro-inflammatory cytokine production in response to toll-like receptor-4 activation, macrophage-stimulating protein strongly suppresses nitric oxide synthase and at the same time upregulates arginase, which is the rate limiting enzyme in the ornithine biosynthesis pathway. Interestingly, RON signaling preserved some of the characteristics of the M1 state, while still promoting the hallmarks of M2 polarization. Therefore, therapeutic modulation of RON activity can shift the activation state of macrophages between acute and chronic inflammatory states.
Frontiers in Immunology 10/2014; 5:546. DOI:10.3389/fimmu.2014.00546
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