Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the gene structure, regulation, signal transduction. and functions of a cytokine, interleukin (IL)-32. An IL-18 unresponsive cell was converted to a responsive cell by transfection of the IL-18 receptor beta chain, and IL-18-induced microarray revealed high expression of a cytokine-like gene. Although IL-32 does not share sequence homology with known cytokine families, IL-32 induces various cytokines, human TNFalpha, and IL-8 in THP-1 monocytic cells as well as mouse TNFalpha and MIP-2 in Raw macrophage cells. IL-32 activates typical cytokine signal pathways of nuclear factor-kappa B (NF-kappaB) and p38 mitogen-activated protein kinase. IL-32 mRNA is highly expressed in immune tissue rather than other tissues. Human IL-32 exists as four splice variants, and IL-32 from other species were found as expressed sequence tag clones in the databank. Induced in human peripheral lymphocyte cells after mitogen stimulation, in human epithelial cells by IFNgamma, and in NK cells after exposure to the combination of IL-12 plus IL-18, IL-32 may play a role in inflammatory/autoimmune diseases.
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PMID:Interleukin-32: a cytokine and inducer of TNFalpha. 1566 65

Pseudomonas aeruginosa is a common organism associated with bacterial keratitis primarily resulting from contact lens usage. Advances in our understanding of host innate and adaptive immune responses to experimental infection have been achieved using animal models, including inbred mouse models that are classed as resistant (cornea heals) vs. susceptible (cornea perforates). Evidence has shown that sustained IL-12-driven IFN-gamma production in dominant Th1 responder strains such as C57BL/6 (B6) contributes to corneal destruction and perforation. In contrast, in Th2-responder BALB/c mice, IL-18-driven IFN-gamma production regulates bacterial killing with less corneal destruction. IL-1 and chemotactic cytokines (e.g., MIP-2) recruit PMN to the cornea. The critical role of these cells in the innate immune response and their regulation after bacterial infection has been established. The studies provide a better understanding of the regulatory mechanisms that operate in the cornea after P. aeruginosa challenge, determining susceptibility vs. resistance to disease, and are consistent with long-term goals of providing targets for better treatment of disease.
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PMID:Role of innate and adaptive immunity in the pathogenesis of keratitis. 1601 72

We examined mRNA expression of 11 genes: BAK, Bcl-x, Interferon [IFN]-gamma, Interleukin [IL]-1beta, IL-6, IL-10, IL-12alpha, IL-12beta, IL-18, CXCLi2 [IL-8/CAF], and a MIP family chemokine, CCLi2, in the spleen and cecum of day-old chicks after oral inoculation with Salmonella enteritidis (SE) or medium. Three distinct chicken breeds (broiler, Fayoumi, and Leghorn) were evaluated for mRNA expression levels at 2 and 18h post-inoculation using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). SE exposure significantly increased splenic IL-18 and IFN-gamma expression. Breed effect was significant (P<0.05) for CXCLi2, IL-10, IL-12alpha, and CCLi2 mRNA expression in the spleen, and for IL-12alpha, IL-12beta, IL-18, and CCLi2 mRNA expression in the cecum. Generally, mRNA expression levels were higher in the spleen, and lower in the cecum, of Leghorns versus broilers. These results support a role for breed genetics influencing cytokine mRNA expression in young chickens and may potentially explain some generalized immune response differences between breeds.
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PMID:Breed effect on early cytokine mRNA expression in spleen and cecum of chickens with and without Salmonella enteritidis infection. 1676 13

Pseudomonas aeruginosa keratitis destroys the cornea in susceptible Th1 responder C57BL/6 (B6), but not resistant Th2 responder (BALB/c) mice. To determine whether single Ig IL-1R-related molecule (SIGIRR) played a role in resistance, mRNA and protein expression levels were tested. Both were constitutively expressed in the cornea of the two mouse groups. A disparate mRNA and protein expression pattern was detected in the cornea of BALB/c vs B6 mice after infection. SIGIRR protein decreased significantly in BALB/c over B6 mice at 1 day postinfection. Thus, BALB/c mice were injected with an anti-SIGIRR Ab or IgG control. Anti-SIGIRR Ab over control-treated mice showed increased corneal opacity, stromal damage, and bacterial load. Corneal mRNA levels for IL-1beta, MIP-2, IL-1R1, TLR4, IL-18, and IFN-gamma and protein levels for IL-1beta and MIP-2 also were significantly up-regulated in anti-SIGIRR Ab over control mice, while no changes in polymorphonuclear cell number, IL-4, or IL-10 mRNA expression were detected. To further define the role of SIGIRR, RAW264.7 macrophage-like cells were transiently transfected with SIGIRR and stimulated with heat-killed P. aeruginosa or LPS. SIGIRR transfection significantly decreased mRNA levels for IL-1R1, TLR4, and type 1 immune response-associated cytokines (IL-12, IL-18, and IFN-gamma) as well as proinflammatory cytokines IL-1beta and MIP-2 protein expression. SIGIRR also negatively regulated IL-1 and LPS, but not poly(I:C)-mediated signaling and NF-kappaB activation. These data provide evidence that SIGIRR is critical in resistance to P. aeruginosa corneal infection by down-regulating type 1 immunity, and that it negatively regulates IL-1 and TLR4 signaling.
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PMID:SIGIRR promotes resistance against Pseudomonas aeruginosa keratitis by down-regulating type-1 immunity and IL-1R1 and TLR4 signaling. 1678 52

Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture system of endometrial stromal cells with first-trimester trophoblast explants was established. Trophoblast and endometrial stromal cells were separated after 24 h. Gene expression of endometrial stromal cells after coculture was compared with the gene expression of endometrial stromal cells cultured alone by microarray analysis. We confirmed the expression of distinct genes using real-time PCR. Genes up-regulated included those for inflammatory response, immune response, and chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL-18 receptor, IL-15, IL-15 receptor, TNF-alpha-induced protein 6, and IL-6 signal transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal transduction. Also up-regulated were genes for growth and development, glucose metabolism, and lipid metabolism: DKK-1, WISP, IGF-II, hydroxysteroid 11beta-dehydrogenase 1, hydroxyprostaglandin dehydrogenase 15, prostaglandin E synthase, prostaglandin F receptor, aldehyde dehydrogenase 1 family, member A3 and phosphatidic acid phosphatase type 2B. Other genes included genes for cell-cell signaling (pre-B-cell colony-enhancing factor 1), proteolysis, calcium ion binding, regulation of transcription, and others. Down-regulated genes included genes for proteolysis (MMP-11 and mitochondrial intermediate peptidase), genes for cell death (caspase 6, death-associated protein kinase 1, and histone deacetylase 5), transcription factors (sex determining region Y-box 4, dachshund homolog 1, ets variant gene 1, and zinc finger protein 84 and 435), and genes for humoral immune response (CD24 antigen). Trophoblast has a significant impact on endometrial stromal cell gene expression. Some of the genes regulated by trophoblast in endometrial stromal cells are already known to be regulated by progesterone and show the endocrine function of trophoblast during pregnancy. Others are genes so far unknown to play a role in endometrial-trophoblast interaction and open a wide field of investigation.
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PMID:Gene expression profiling of human endometrial-trophoblast interaction in a coculture model. 1694 11

Influenza A virus is one of the most important causes of respiratory tract diseases. It replicates in epithelial cells and leukocytes resulting in the production of immune mediators--cytokines, substances with various biological effects. Cytokines, as a part of innate immunity, favor the development of antiviral and TH 1-type immune responses. Cytokines also affect the adaptive immune response and disease manifestation. In the organism, the virus infection results in the production of chemotactic [a regulated upon activation, normal T cell-expressed and -secreted cytokine (RANTES), monocyte chemoattractant proteins (MCP) MCP-1, MCP-3, macrophage inflammatory protein 1 alpha (MIP- 1 alpha), interferon gamma-induced protein 10 (IP-10), and interleukin 8 (IL-8)], pro-inflammatory [IL- 1beta, IL-6, IL-18, and tumor necrosis factor alpha(TNF-alpha)] and antiviral [interferon (IFN) alpha/beta] cytokines. Whilst knowledge of the mechanisms underlying host and tissue specificity has advanced significantly, we still know relatively little about the function of cytokines released from different cells following influenza infection. In this review we deal with the role and mode of possible impact of cytokines on the disease pathogenesis and host immune response.
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PMID:The role of cytokines in the immune response to influenza A virus infection. 1713 33

We have investigated the mechanisms underlying IL-15-induced neutrophil migration into inflamed tissues. IL-15 induced neutrophil migration to the peritoneal cavity in mice in a time- and dose-dependent manner. The cell migration was not induced in IL-18-/-, MIP-1alpha (CCL3)-/-, TNFR1-/- or 5-LOX-/- mice but was normal in IFN-gamma-/- mice. IL-15-induced neutrophil migration was inhibited by anti-MIP-2 (CXCL2) antibody or MK886 (leukotriene synthesis inhibitor). IL-18-induced neutrophil migration was also dependent on TNFR1, MIP-1alpha, MIP-2 and leukotriene. Consistent with this observation, IL-15 induced IL-18 production, and IL-15 or IL-18 injection induced the production of MIP-2, MIP-1alpha, TNF-alpha and LTB4. In an antigen-specific inflammation model, ovalbumin (OVA)-induced neutrophil migration was completely inhibited by soluble IL-15Ralpha (sIL-15Ralpha) or anti-MIP-2 antibody. Furthermore, cell migration was absent in IL-18-/-, MIP-1alpha-/-, TNFR1-/-, or 5-LOX-/- mice. OVA challenge induced the release of MIP-2, MIP-1alpha, TNF-alpha and LTB4 in the peritoneal cavity in an IL-15- and IL-18-dependent manner. We also found that neutrophils from the peripheral blood and synovial fluid of patients with rheumatoid arthritis produced substantial amounts of IL-18 and LTB4 following activation by IL-15. Together, these results demonstrate that IL-15 plays an important role in antigen-induced neutrophil migration during inflammation, triggering a sequential OVA, IL-15, IL-18, MIP-2, MIP-1alpha, TNF-alpha, LTB4 and neutrophil migration signaling cascade.
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PMID:IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. 1797 56

The IL-1 family member 7b (IL-1F7b) is a novel homolog of the IL-1 cytokine family discovered by computational cloning. We have reported that IL-1F7b shares critical amino acid residues with IL-18 and binds the IL-18-binding protein; in doing so, IL-1F7b augments the inhibition of IFN-gamma by the IL-18-binding protein. IL-1F7b also binds IL-18Ralpha but neither induces signal nor acts as a receptor antagonist. Hence, the function of IL-1F7b remains unknown. In the present study, we analyzed the intracellular expression pattern of IL-1F7b. Using two variants of GFP fusion constructs of human IL-1F7b stably expressed in RAW macrophages, only the postcleavage mature form of the IL-1F7b precursor-but not the N-terminal propiece-specifically translocates to the nucleus following LPS stimulation. IL-1F7b, like IL-1beta, IL-18, and IL-33, is processed by caspase-1 to generate the mature cytokines. Therefore, we tested whether caspase-1-mediated cleavage of the IL-1F7b precursor is required for mature IL-1F7b to translocate actively into the nucleus. Indeed, a specific caspase-1 inhibitor markedly reduced nuclear entry of IL-1F7b. In stable transfectants of human IL-1F7b in RAW macrophages stimulated with LPS, levels of TNF-alpha, IL-1alpha, IL-6, as well as the chemokine MIP-2, were substantially reduced (72-98%) compared with LPS-stimulated cells transfected with the empty plasmid. These results demonstrate that IL-1F7b translocates to the nucleus after caspase-1 processing and may act as a transcriptional modulator reducing the production of LPS-stimulated proinflammatory cytokines, consistent with IL-1F7b being an anti-inflammatory member of the IL-1 family.
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PMID:The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines. 1839 Jul 30

Earlier, we demonstrated that intramuscular administration of oligodeoxynucleotides containing CpG motifs (CpG-ODN) induces protection in neonatal chicks against a lethal challenge of Escherichia coli. However, the mechanism of induction of the protection was not clear. In an attempt to elucidate the mechanism of induced protection, we determined the kinetics of expression of cytokines/chemokines in the spleen and bursa of Fabricius of newly hatched chicks that had received intramuscular administration of CpG-ODN or non-CpG ODN compared to saline-treated controls. SyBr green, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis of the RNA demonstrated increased expression of IL-1beta, IL-6, IL-8, IL-10, IL-18, IFN-gamma and MIP-3alpha mRNAs in the spleen and; IL-10 and IFN-alpha in bursa of Fabricious of chicks that had received CpG-ODN. However, non-CpG ODN failed to induce any of the cytokine. The increased level of IL-18 and IFN-gamma but not IL-4 mRNA suggests that the administration of CpG-ODN elicits a Th1 biased immune response, which may be important in inducing protection against infections in neonatal chicks. To our knowledge, this is the first report evaluating the induction of cytokines/chemokines in neonatal chicks following administration of CpG-ODN.
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PMID:Oligodeoxynucleotides containing CpG motifs (CpG-ODN) predominantly induce Th1-type immune response in neonatal chicks. 1839 55

Previously, we have found that a prior burn insult induces lethal acute lung injury (ALI) and overproduction of proinflammatory cytokines after LPS challenge in mice. The current study was aimed to determine the role of IL-18 in burn-induced LPS hypersensitivity. Except sham group, mice were subjected to a 15% total body surface area full-thickness burn and either untreated or treated with IL-18 alone, IL-18 + anti-IL-10 antibody or IL-18 + isotype immunoglobulin G. LPS was intravenously administered to all mice on the 11th day, and the mice were killed at the indicated time point, or survival was examined. We additionally examined cytokine production by splenic cells in vitro for the elucidation of immunologic mechanisms. Unexpectedly, the liver IL-18 decreased transiently after burn injury, and in vivo IL-18 supplementation improved survival and ameliorated ALI, as well as reducing the lung contents of all cytokines examined, except IL-10. Neutralization of IL-10 cancelled the protective effect of IL-18. In splenic macrophages obtained from burned mice, the production of macrophage inflammatory protein 2 (MIP-2), TNF-alpha, and IL-10 was augmented, whereas in vivo IL-18 supplementation decreased MIP-2 production, but increased IL-10 production. Furthermore, a physiological concentration of IL-18 directly attenuated MIP-2 production by splenic cells in vitro. Burn injury induces LPS hypersensitivity through augmented production of proinflammatory cytokines by systemic macrophages. IL-18 supplementation is protective for LPS-induced lethal ALI through the direct anti-inflammatory effect on macrophages as well as by in vivo acceleration of IL-10 production, and could thus be an effective prophylactic strategy against septic complications in critically ill patients.
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PMID:In vivo IL-18 supplementation ameliorates lethal acute lung injury in burn-primed endotoxemic mice: a novel anti-inflammatory role of IL-18. 1919 24


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