Disease relevance of Il18bp

• Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response [1].
• We confirm that molluscum contagiosum virus, a molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L) [1].
• The MC51L, MC53L, and MC54L open reading frames of MCV have significant amino acid sequence similarities and related proteins are encoded by other poxviruses [2].
• Identification of residues in an orthopoxvirus interleukin-18 binding protein involved in ligand binding and species specificity [3].
• Because p13 can bind both human and murine IL-18, and because it is highly homologous to the variola virus IL-18BP, we set out to identify residues that may be involved in species specificity [3].

High impact information on Il18bp

• Several Poxviruses encode putative proteins highly homologous to IL-18BP, suggesting that viral products may attenuate IL-18 and interfere with the cytotoxic T cell response [4].
• By neutralizing IL-18 activity with IL-18 binding protein (IL-18BP), we observed that islets produce bioactive IL-18 [5].
• In vivo, transgenic mice overproducing IL-18BP (IL-18BP-Tg) exhibited delayed hyperglycemia induced by beta cell toxic streptozotocin [5].
• In testing whether IL-1F7b interacts with IL-18BP, we unexpectedly observed that IL-1F7b enhanced the ability of IL-18BP to inhibit IL-18-induced IFNgamma by 25-30% in a human natural killer cell line [6].
• Molecular modeling identified a large mixed electrostatic and hydrophobic binding site in the Ig domain of IL-18BP, which could account for its high affinity binding to the ligand [7].

Biological context of Il18bp

• More importantly, transfection with the IL-18BP plasmid induces profound changes in plaque composition (decrease in macrophage, T cell, cell death, and lipid content and increase in smooth muscle cell and collagen content) leading to a stable plaque phenotype [8].
• The murine interleukin-18 binding protein cDNA was cloned after RT-PCR using mixed primer pair sequences based on partial murine interleukin-18 binding protein amino acid sequence analysis [9].
• Using point mutagenesis, we analyzed the ectromelia virus IL-18BP to identify residues involved in binding [3].
• Subsequently, human interleukin-18 binding protein cDNA was cloned from cDNA libraries of normal human liver using murine interleukin-18 binding protein cDNA as a probe [9].
• Ischemia was produced by artery femoral occlusion in mice that were subjected to in vivo intramuscular electrotransfer of either an empty plasmid or a murine IL-18BP plasmid [10].

Anatomical context of Il18bp

• Interleukin-18/interleukin-18 binding protein signaling modulates ischemia-induced neovascularization in mice hindlimb [10].
• IL-18BP and TCR gamma delta cells appear to be critical factors in the anti-inflammatory effects of IRF-1 [11].
• Twelve hours after IL-18BP, hepatic sinusoidal endothelium (HSE) cells were isolated, and adhesion of B16M cells to these cultured HSE cells was reduced to the level of vehicle-treated mice [12].

Associations of Il18bp with chemical compounds

• Interleukin-18 binding protein is a novel glycoprotein that we successfully cloned and expressed [9].

Regulatory relationships of Il18bp

• INTERVENTIONS: We sought to determine the role of interleukin-18 in sepsis by blocking its biological activity with the interleukin-18 binding protein in the murine model of sepsis induced by cecal ligation and puncture [13].

Other interactions of Il18bp

• Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability [8].
• Although infection leads to increased expression of IL-18BP mRNA, no difference was seen between WT and IL-10-/- mice [14].
• Mice were subjected to cecal ligation and puncture and, on the basis of the plasma concentration of interleukin-6, were randomized to receive either interleukin-18 binding protein or vehicle approximately 8 hrs after the onset of sepsis [13].
• These include endogenous IL-18 binding protein (IL-18BP), CXCL16 (the ligand of Bonzo, CXCR6) as well as ESTs [15].

Analytical, diagnostic and therapeutic context of Il18bp

• Angiographic score, capillary density (CD31 staining), and laser Doppler perfusion data at day 28 showed significant improvement in ischemic/nonischemic leg ratio by respectively 1.6-, 1.4-, and 1.5-fold in IL-18BP-treated mice compared with controls (P<0.01) [10].
• Using this monoclonal antibody, we have developed an ELISA for determining IL-18BP levels [16].

References