Immunomodulatory Functions (immunomodulatory + function)

Distribution by Scientific Domains

Selected Abstracts

Conserved fate and function of ferumoxides-labeled neural precursor cells in vitro and in vivo

Mikhal E. Cohen
Abstract Recent progress in cell therapy research for brain diseases has raised the need for non-invasive monitoring of transplanted cells. For therapeutic application in multiple sclerosis, transplanted cells need to be tracked both spatially and temporally, in order to assess their migration and survival in the host tissue. Magnetic resonance imaging (MRI) of superparamagnetic iron oxide-(SPIO)-labeled cells has been widely used for high resolution monitoring of the biodistribution of cells after transplantation into the central nervous system (CNS). Here we labeled mouse glial-committed neural precursor cells (NPCs) with the clinically approved SPIO contrast agent ferumoxides and examined their survival and differentiation in vitro, as well as their functional response to environmental signals present within the inflamed brain of experimental autoimmune encephalomyelitis (EAE) mice in vivo. We show that ferumoxides labeling does not affect NPC survival and pluripotency in vitro. Following intracerebroventricular (ICV) transplantation in EAE mice, ferumoxides-labeled NPCs responded to inflammatory cues in a similar fashion as unlabeled cells. Ferumoxides-labeled NPCs migrated over comparable distances in white matter tracts and differentiated equally into the glial lineages. Furthermore, ferumoxides-labeled NPCs inhibited lymph node cell proliferation in vitro, similarly to non-labeled cells, suggesting a preserved immunomodulatory function. These results demonstrate that ferumoxides-based MRI cell tracking is well suited for non-invasive monitoring of NPC transplantation. 2009 Wiley-Liss, Inc. [source]

ORIGINAL ARTICLE: Effect of Progesterone on HLA-E Gene Expression in JEG-3 Choriocarcinoma Cell Line

Zhongying Huang
Problem, Among class Ib human leukocyte antigen (HLA) molecules, HLA-E is known to be a major ligand of CD94/NKG2 receptor on natural killer (NK) cells, and to play a pivotal role in recognition of extravillous trophoblasts (EVTs) by maternal immune cells. However, it is scarcely known how HLA-E expression is regulated in EVTs. Method of study, In this study, we investigated whether progesterone, an essential hormone in maintaining pregnancy, regulated HLA-E expression in EVT-like cell line, JEG-3. HLA-E mRNA amount in cultured JEG-3 cells was assessed by real-time PCR and cell-surface HLA-E protein was analyzed by flowcytometry. Results, Real-time PCR showed 3.5-fold increase 1 hour after the addition of 1000 ng/ml progesterone. This response was dimished by the addition of RU486, an antagonist for progesterone receptor. Flowcytometry indicated that 1000 ng/ml progesterone slightly enhanced HLA-E expression on the surface of JEG-3. Conclusion, These results suggest that progesterone up-regulates HLA-E expression in JEG-3 cells through the pathway mediated by progesterone receptor. Our findings might give a new insight into immunomodulatory function of progesterone at fetomaternal interface. [source]

Expression profiling of IL-10-regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL-10 therapy

Mechthild Jung
Abstract Interleukin-10 (IL-10), originally identified as an inhibitor of pro-inflammatory cytokine production, exerts multiple immunomodulatory functions. Its ability to inhibit a Th1 response has been used in clinical trials for the treatment of inflammatory diseases including psoriasis. However, little is known about the molecular mechanisms of IL-10 functions. We aimed at identifying possiblemediators of in vitro IL-10 treatment in monocytes by gene chip technology using Hu95a Affymetrix mRNA arrays with,12,000 genes. To prove relevance of the identified genes for the clinicalsituation we compared these in vitro results with genes being regulated by IL-10 in peripheral blood mononuclear cells from psoriatic patients undergoing IL-10 therapy. A high proportion of the 1,600,genes up-regulated and 1,300 genes down-regulated in vitro was found to be similarly regulated in vivo. Some genes, which were previously unknown to be regulated by IL-10, can be assigned to known IL-10 functions like e.g. the increase of pathogen clearance. Other new potentially immunomodulating genes have been identified to be regulated by IL-10, but their impact needs to be experimentally evaluated. We could confirm a recently reported up-regulation of heme oxygenase-1 (HO-1). However, we demonstrate that the anti-inflammatory mechanisms of IL-10 remain functional even when HO-1 is irreversibly inhibited. [source]

The role of type I interferons in non-viral infections

Christian Bogdan
Summary:, For a long time, the family of type I interferons (IFN-,/,) has received little attention outside the fields of virology and tumor immunology. In recent years, IFN-,/, regained the interest of immunologists, due to the phenotypic and functional characterization of IFN-,/,-producing cells, the definition of novel immunomodulatory functions and signaling pathways of IFN-,/,, and the observation that IFN-,/, not only exerts antiviral effects but is also relevant for the pathogenesis or control of certain bacterial and protozoan infections. This review summarizes the current knowledge on the production and function of IFN-,/, during non-viral infections in vitro and in vivo. [source]

Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid- , peptide in rat brain: a comparative, in vivo study versus vitamin C and E

Sergio Rosales-Corral
Abstract: To determine the efficacy of antioxidants in reducing amyloid- , -induced oxidative stress, and the neuroinflammatory response in the central nervous system (CNS) in vivo, three injections of fibrillar amyloid- , (fA,) or artificial cerebrospinal fluid (aCSF) into the CA1 region of the hippocampus of the rat were made. Concomitantly, one of the three free radical scavengers, i.e. melatonin, vitamin C, or vitamin E was also administered. Besides being a free radical scavenger, melatonin also has immunomodulatory functions. Antioxidant treatment reduced significantly oxidative stress and pro-inflammatory cytokines. There were no marked differences between melatonin, vitamin C, and vitamin E regarding their capacity to reduce nitrites and lipoperoxides. However, melatonin exhibited a superior capacity to reduce the pro-inflammatory response induced by fA,. [source]

Immune escape and exploitation strategies of cytomegaloviruses: impact on and imitation of the major histocompatibility system

Edward S. Mocarski Jr
Summary Cytomegalovirus (CMV) has yielded many insights into immune escape mechanisms. Both human and mouse CMV encode a diverse array of gene products, many of which appear to modulate the immune response in the host. Some deflect the host response to infection and contribute to lifelong viral persistence while others exploit immune cells that respond to infection. Here, the viral functions that modulate and mimic host major histocompatibility complex (MHC) function will be reviewed. Viral gene products related to both classical and non-classical components of the MHC system assure the virus will persist in immunocompetent individuals. Examples of host countermeasures that neutralize viral immunomodulatory functions have emerged in the characterization of viral functions that contribute to this stand-off in CMVs that infect humans, other primates and rodents. CMV-induced disease occurs when the immune system is not yet developed, such as in the developing fetus, or when it is compromised, such as in allograft transplant recipients, suggesting that the balance between virus escape and host control is central to pathogenesis. Although evidence supports the dominant role of immune escape in CMV pathogenesis and persistence, MHC-related immunomodulatory functions have been ascribed only subtle impact on pathogenesis and the immune response during natural infection. Viral gene products that interface with the MHC system may impact natural killer cell function, antigen presentation, and T lymphocyte immune surveillance. Many also interact with other cells, particularly those in the myeloid lineage, with consequences that have not been explored. Overall, the virus-encoded modulatory functions that have been acquired by CMV likely ensure survival and adaptation to the wide range of mammalian host species in which they are found. [source]