Zhang and colleagues explored the immunomodulatory activity of the cholesterol-lowering agent simvastatin. Their pharmaco-dynamic studies indicated that the immuno-modulatory activity of statins may involve two basic mechanisms. First, it may involve an increase in SOCS-3 and SOCS -7, i.e. members of the molecular family of “Suppressors of Cytokine Secretion”. And second, it may involve the inhibition of Interleukin-17 (IL-17), a central pro-inflammatory mediator.
The members of the SOCS family of molecules are important negative feedback regulators in adaptive and innate immune responses, while IL-17 producing CD4+ cells, the so-called “Th17 cells”, play a central role in the development of autoimmune diseases.
From their findings the authors conclude as follows: “Based on the described immunomodulatory mechanisms, good safety profile and oral biovailabalility, statins represent a promising therapeutic approach for multiple sclerosis and other chronic inflammatory diseases.”
Along the lines of this study by Zhang and colleagues, FOCUS Immunology is prepared to provide state-of-the-art services for pharmacodynamic (PD) analyses of immuno-modulatory compounds under GLP conditions.
If you are interested in learning more or in discussing your specific experimental needs, please feel free to contact Dr. Eddy Bruyns, Head of FOCUS Immunology Laboratory via e-mail eddy.bruyns@focus-cdd.com or via telephone +49 6221 64935124.
Source
Zhang et al.
Simvastatin Inhibits IL-17 Secretion by Targeting Multiple IL-17-Regulatory Cytokines and by Inhibiting the Expression of IL-17 Transcription Factor RORC in CD4+ Lymphocytes
The Journal of Immunology 2008; 180; 6988-6996
Hyperactivation of the immune system can lead to tissue destruction and auto-immunity. Therefore, the amplitude and duration of immune responses after antigenic and cytokine signaling are regulated in a feedback manner.
So-called “Suppressors of Cytokine Signaling (SOCS)” are important molecular players in this negative feedback regulation. 7 members of the SOCS molecular family have been described so-far. The SOCS family members 1 and 3 are of particular importance, since they are involved in adaptive and innate immune responses.
SOCS-1 and -3 are induced by LPS stimulation via the Toll-like Receptor-4 (TLR-4). While SOCS-1 directly targets the downstream signaling molecules of TLR4, SOCS-3 regulates the secondary effects of many LPS-induced cytokines. E.g. IL-1R signalling pathways are negatively regulated by SOCS-3.
In adaptive immune responses SOCS-1 and -3 play a role in the regulation of T cell activation, proliferation and diferentiation.
Recently, SOCS molecules were found to be central elements in the pharmacodynamics of the immuno-modulatory compound simvastatin and probiotic lactobacilli.
FOCUS Immunology is prepared to provide state-of-the-art services for pharmacodynamic (PD) studies for immunomodulatory compounds under GLP conditions. This includes studies on the regulation of intra- and extracellular mediators of inflammationand immunity.
If you are interested in learning more about FOCUS Immunology’s experience and offers or if you want to discuss your specific experimental needs, please feel free to contact Dr. Eddy Bruyns, Head of FOCUS Immunology Laboratory via e-mail eddy.bruyns@focus-cdd.com or via telephone +49 6221 64935124.
Source
Dimitriou et al.
Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins
Immunological reviews 2008, Vol. 224: 265-283
More information on SOCS1: Wikipedia on SOCS1
More information on SOCS3: Wikipedia on SOCS3
Suppressors of Cytokine Signaling (SOCS) are a group of proteins that play an important role in attenuating immune responses. These molecules may thus be important players in the pharmacodynamics (PD) of immuno-modulatory therapies.
In a recent publication Lee and colleagues explored whether probiotics induced anti-inflammatory properties through induction of SOCS.
Helicobacter pylori (H. pylori) or lipopolysaccharides derived thereof were found to increase the expression of pro-inflammatory cytokines in a human gastric cell line. Pre-treatment of the cells with probiotic bacteria of the Lactobacillus group reduced the H.Pylori-induced expression of these cytokines.
When the underlying molecular mechanisms were explored in more detail, the administration of probiotics was found to increase the expression of SOCS-2 and SOCS-3.
The authors conclude that the “Anti-inflammatory signals of SOCS … might be a key anti-inflammatory mechanism of probiotics …”
FOCUS Immunology is prepared to provide state-of-the-art servcies for pharmacodynamic (PD) studies for immunomodulatory compounds under GLP conditions.
If you are interested in learning more about FOCUS Immunology’s experience and offers or if you want to discuss your specific experimental needs, please feel free to contact Dr. Eddy Bruyns, Head of FOCUS Immunology Laboratory via e-mail eddy.bruyns@focus-cdd.com or via telephone +49 6221 64935124.
Source
Jeong Sang Lee et al.
Anti-inflammatory actions of probiotics through activating suppressor of cytokine signaling (SOCS) expression and signaling in Helicobacter pylori infection: A novel mechanism
Journal of Gastroenterology and Hepatology 25 (2010) 194-202
Natural Killer (NK) cells play an important role in anti-viral and anti-tumor immune responses. NK cells appear to be involved in many pathologies and many therapeutic strategies involve the modulation of NK cell activity.
FOCUS Immunology has established state-of-the art protocols for the phenotypic and functional analysis of NK cells.
For further information on our expertise in NK cell biology please contact us at immunology@focus-cdd.com or contact directly our Head of FOCUS Immunology Dr. Eddy Bruyns at eddy.bruyns@focus-cdd.com.
FOCUS Immunology laboratory is part of the Clinical Research Organisation (CRO) FOCUS-CDD GmbH. FOCUS Immunology provides immunological biomarker services under GLP and non-GLP conditions for the development of novel medicines.
The innate or non-specific immune system provides immediate defence reactions against invading pathogens. Granulocytes, monocytes/macrophages, NK-cells, mast cells and dendritic cells are important cellular constituents of the innate immune system.
Cells of the innate immune system do not possess antigen-specific receptors but instead recognize conserved molecules expressed by large numbers of microorganisms. These conserved molecules are referred to as pathogen-associated molecular patterns or PAMPS and the corresponding receptors on cells of the innate immune system are called pattern-recognition receptors or PRRs.
Toll-like receptors (TLR) are an example for PRRs. TLRs recognize different types of molecules expressed by bacteria, viruses, fungi and protozoa. Extensive research has allowed correlating TLRs with the molecules they recognize: e.g. the endotoxin LPS, which is widely expressed by gram negative bacteria, is recognized by TLR 4, while unmethylated CpG-DNA sequences, which distinguishes bacterial DNA from mammalian DNA, is recognized by TLR-9.
FOCUS Immunology has established a complete range of assays to functionally analyse the triggering of TLRs and the subsequent activation of the respective cell.
Ligands for the 9 well characterized human TLRs (TLR1 – TLR9) are used to stimulate Peripheral Blood Mononuclear Cells (PBMC) in vitro and analyze the secretion of the cytokine TNF-alpha.
This assay allows analyzing the effect any compound, whether NCE or NBE, may have on TLR-mediated stimulation of cells of the innate immune system.
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Friday, July 2, 2010
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