Gene set analysis suggested up-regulation of a variety of pr......
Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).More...
Positive relationships between IL18 and other components at different levels (count: 0)
Positive relationship network of IL18 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
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If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
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Negative relationships between IL18 and MDD (count: 0)
Negative relationships between IL18 and other components at different levels (count: 0)
Cytokines are soluble extracellular proteins or glycoprotein......
Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Cytokines are released by various cells in the body, usually in response to an activating stimulus, and they induce responses through binding to specific receptors on the cell surface of target cells. Cytokines can be grouped by structure into different families and their receptors can likewise be grouped.More...
Specific families of pattern recognition receptors are respo......
Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-{kappa}B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. These NLRs include NALP1, NALP3 and Ipaf. The inflammasomes are critical for generating mature proinflammatory cytokines in concert with Toll-like receptor signaling pathway.More...
Specific families of pattern recognition receptors are respo......
Specific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified sensor of cytosolic DNA which activates the IRF and NF-{kappa}B transcription factors, leading to production of type I interferon and other cytokines. The second type of cytoplasmic DNA sensor is AIM2. Upon sensing DNA, AIM2 triggers the assembly of the inflammasome, culminating in interleukin maturation. In addition to these receptors, there is a mechanism to sense foreign DNA, with the host RNA polymerase III converting the DNA into RNA for recognition by the RNA sensor RIG-I. These pathways provide various means to alert the cell.More...
Ras-Independent pathway in NK cell-mediated cytotoxicity
NK (natural killer) cells are lymphocytes distinct from B an......
NK (natural killer) cells are lymphocytes distinct from B and T cells that induce perforin-mediated lysis of tumor cells and virus-infected cells. NK cell-mediated cytotoxicity is activated by glycoproteins on the cell surface (activating receptors) and inhibited by MHC-1 with self-peptide bound. The MHC-1 inhibitory signal through Ig-family or lectin receptors prevents NK cells from killing normal cells. Abnormal MHC-1 expression in infected or tumor cells results in the release of perforin, the lysis of the abnormal cell and the release of cytokines that stimulate the immune response. MAP kinase inhibitors but not ras inhibitors are able to block NK cell cytotoxicity, indicating that the pathway can function by a ras-independent manner that involves the MAP kinase pathway. This pathway includes phosphoinositide-3-kinase (PI3K) as a key component, followed by Rac1 and the exchange factor Vav. The tyrosine kinase SYK and LAT may provide an additional pathway for activation of MAP kinases leading to NK cell activation, and also Pyk-2 activation by integrins. The protein tyrosine phosphatase SHP-1 appears to mediate the cytotoxicity inhibitory signal that blocks lysis of normal cells. The balance of these positive and negative signaling pathways regulates the role of NK cells in the immune response.More...
Several different cell types coordinate their efforts as par......
Several different cell types coordinate their efforts as part of the immune system, including B cells, T cells, macrophages, neutrophils, basophils and eosinophils. Each of these cell types has a distinct role in the immune system, and communicates with other immune cells using secreted factors called cytokines, including interleukins, TNF, and the interferons. Macrophages phagocytose foreign bodies and are antigen-presenting cells, using cytokines to stimulate specific antigen dependent responses by B and T cells and non-specific responses by other cell types. T cells secrete a variety of factors to coordinate and stimulate immune responses to specific antigen, such as the role of helper T cells in B cell activation in response to antigen. The proliferation and activation of eosinophils, neutrophils and basophils respond to cytokines as well. Cytokine communication is often local, within a tissue or between cells in close proximity. Each of the cytokines is secreted by one set of cells and provokes a response in another target set of cells, often including the cell that secretes the cytokine. Some cytokines, like IL-1, interferons and TNF, stimulate a broad inflammatory response in response to infection or injury. Other cytokines have more specific functions such the following examples. IL-2 stimulates the proliferation and activation of B and T cells. IL-4 plays a role in the differentiation of Th2 cells, in allergic responses, and in the switching of antibody types. IL-5 stimulates the production and maturation of eosinophils during inflammation. IL-8 is a chemokine, a chemotactic factor that attracts neutrophils, basophils and T cells to sites of inflammation. IL-12 and IL-18 are involved in helper T cell differentiation. IL-10 apparently acts to repress secretion of proinflammatory cytokines. The complex interplay of these different cytokine functions with immune cells is essential for correct immune function.More...
Helper T cells are found in two distinct cell types, Th1 and......
Helper T cells are found in two distinct cell types, Th1 and Th2, distinguished by the cytokines they produce and respond to and the immune responses they are involved in. Th1 cells produce pro-inflammatory cytokines like IFN-g, TNF-b and IL-2, while Th2 cells produce the cytokines IL-4, IL-5, IL-6 and IL-13. The cytokines produced by Th1 cells stimulate the phagocytosis and destruction of microbial pathogens while Th2 cytokines like IL-4 generally stimulate the production of antibodies directed toward large extracellular parasites. IL-5 stimulates eosinophil responses, also part of the immune response toward large extracellular parasites Th1 and Th2 are produced by differentiation from a non-antigen exposed precursor cell type, Thp. Exposure of Thp cells to antigen by antigen-presenting cells may result in their differentiation to Th0 cells, not yet committed to become either Th1 or Th2 cells, although the existence of Th0 cells is controversial. Cells committed as either Th1 and Th2 cells are called polarized, whether they are effector cells actively secreting cytokines or are memory cells. The stimulation of Thp cells by exposure to antigen-presenting cells induces the proliferation of undifferentiated cells, and their expression of IL-2 and IL-2 receptor. The differentiation of Th1 cells and Th2 cells depends on the cytokines they are exposed to. IL-12 causes Th1 differentiation and blocks Th2 cell production , while IL-4 causes Th2 differentiation and antagonizes Th1 development. IL-18 also induces Th1 differentiation. Polarized Th1 and Th2 cells also express distinct sets of chemokine receptors that further modify their homing and other cellular responses. Improved understanding of Th1 and Th2 differentiation will improve our overall understanding of the immune system, its response to infection and aberrant responses that lead to disease.More...
IL12 and Stat4 Dependent Signaling Pathway in Th1 Development
Interleukin-12 (IL-12) promotes cell-mediated immunity by in......
Interleukin-12 (IL-12) promotes cell-mediated immunity by inducing Th1 cell differentiation and activation of both T cells and NK cells. Dendritic cells and macrophages in peripheral tissues act as antigen presenting cells and secrete IL-12 as one component of the antigen response, Th1 differentiation. The role of IL-12 in cellular immunity is largely mediated by the STAT-4 transcription factor. STAT-4 is essential for IL-12 activity and the phenotype of mice lacking STAT-4 is very similar to the phenotype of mice lacking the IL-12 receptor or IL-12. The role of IL-12 in Th1 differentiation may not be to induce the Th1 cell fate, but to stimulate growth of cells determined for the Th1 cell fate by the T-bet transcription factor. Several signaling pathways contribute to IL-12 activation of STAT-4 to regulate cell-mediated immune responses. The JAK kinases such as JAK2 and TYK2 interact with the activated IL-12 receptor and tyrosine phosphorylate the IL-12 receptor and STAT-4. IL-12 also activates a map kinase pathway activating the map kinase kinase MKK6 and p38. Phosphorylation of STAT-4 on serine 721 by p38 contributes to the full transcriptional activation of genes by STAT-4. Some of the events downstream of IL-12 appear to include genes activated indirectly by STAT-4, such as genes activated by the transcription factor ERM. ERM is in the Ets family of transcription factors, is activated by IL-12 and activates IL-12 inducible genes such as Interferon-gamma that are not activated by STAT-4 itself. Interferon-gamma transcription in T cells is also activated by other signals such as from the T cell receptor. Other proteins activated transcriptionally downstream of IL-12 and STAT-4 include the chemokine receptor CCR5 and IL-18 and its receptor. Some viruses, including HIV, repress cell-mediated immunity by blocking IL-12 signaling.More...
IL18 related Reactome pathways (count: 0)
IL18 related interactors from protein-protein interaction data in HPRD (count: 7)
Basic Information
Positive relationships between IL18 and other components at different levels (count: 0)
