Biomedical subjects

Soo-Hyun Kim

Publications and source records attributed to Soo-Hyun Kim.

53 records · Page 3Linked to original sources

PubMed2003

Generation and characterization of mice transgenic for human IL-18-binding protein isoform a.

Interleukin (IL)-18 binding protein (IL-18BP) is a natural inhibitor of the pleiotropic cytokine IL-18. To study the role of IL-18BP in modulating inflammatory responses in vivo, mice transgenic for human IL-18BP isoform a (IL-18BP-Tg) were generated. The transgene was expressed at high levels in each organ examined. High levels of bioactive human IL-18BPa were detectable in the circulation of IL-18BP-Tg mice, which were viable, fertile, and had no tissue or organ abnormality. The high levels of IL-18BP in the transgenic mice were able to completely neutralize the interferon-gamma (IFN-gamma)-inducing activity of exogenously administered IL-18. Following administration of endotoxin, with or without prior sensitization with heat-inactivated Propionibacterium acnes, IL-18BP-Tg mice produced significantly lower serum levels of IFN-gamma and macrophage-inflammatory protein-2 compared with nontransgenic littermates. Significantly reduced production of IFN-gamma in response to endotoxin was also observed in cultures of IL-18BP-Tg splenocytes. Finally, IL-18BP-Tg mice were completely protected in a model of hepatotoxicity induced by administration of concanavalin A. These results indicate that high endogenous levels of IL-18BP in trangenic mice effectively neutralize IL-18 and are protective in response to different inflammatory stimuli.

Animals↗

PubMed2003

Isolation, identification, and quantitation of urinary glycosaminoglycans.

BACKGROUND: Substantial amounts of glycosaminoglycans (GAGs) are present in the urine of healthy individuals, but the concentration in the serum is very low. This finding suggests that urinary GAGs come from the glomerulus and may reflect the turnover of GAGs in the glomerulus. HYPOTHESIS: However, little is known about the physiologic regulation of the urinary GAGs in humans, and so investigations are needed to evaluate the effects of age and sex on urinary GAGs in normal individuals. METHODS: Eighty-seven healthy subjects were included in this study. Urinary GAGs were isolated and quantified at the nanogram level by combined azure A-silver staining in agarose gels. RESULTS: The level of urinary GAGs peaked at 10-19 years in both sexes. The proportion of chondroitin sulfate decreased with age, but the proportion of heparan sulfate increased with age. CONCLUSION: The total amount of GAGs and the proportions of chondroitin sulfate, heparan sulfate, and dermatan sulfate appear to change with age. Therefore, investigations in which urinary GAG is used as a parameter of glomerular GAG turnover should ensure that control groups are precisely matched for age. Changes in the proportions of each GAG may be more informative than their absolute levels.

Adolescent↗

PubMed2003

Mechanisms of inhibition of collagen-induced arthritis by murine IL-18 binding protein.

IL-18 is an important cytokine in autoimmune and inflammatory diseases through the induction of IFN-gamma, TNF-alpha, and IL-1. We report herein that collagen-induced arthritis (CIA) in mice is inhibited by treatment with murine IL-18 binding protein (mIL-18BP). CIA was induced in DBA/1J mice by the injection of bovine type II collagen (CII) in IFA with added Mycobacterium tuberculosis on days 0 and 21. The mice were then treated for 3 wk with PBS or with two doses of mIL-18BP (0.5 and 3 mg/kg) as a fusion protein with the Fc portion of murine IgG1. Both the clinical disease activity scores and the histological scores of joint damage were reduced 50% in mice treated with either dose of mIL-18BP. Proliferation of CII-stimulated spleen and lymph node cells as well as the change in serum levels of IgG1 and IgG2a Ab to collagen between days 21 and 42 were decreased in mice treated with mIL-18BP. The production of IFN-gamma, TNF-alpha, and IL-1beta in cultured spleen cells was reduced by in vivo treatment with low dose, but not high dose, mIL-18BP. FACS analysis showed a slight decrease in NK cells and an increase in CD4(+) T cells in spleens of mice treated with mIL-18BP. The steady state mRNA levels of IFN-gamma, TNF-alpha, and IL-1beta in isolated joints were all decreased in mice treated with both doses of mIL-18BP. The mechanisms of mIL-18BP inhibition of CIA include reductions in cell-mediated and humoral immunity to collagen as well as decreases in production of proinflammatory cytokines in the spleen and joints.

Animals↗

PubMed2003

Regulation of Staphylococcus epidermidis-induced IFN-gamma in whole human blood: the role of endogenous IL-18, IL-12, IL-1, and TNF.

Interleukin 12 (IL-12) and IL-18 act synergistically to stimulate interferon gamma (IFN-gamma) production; moreover, IL-1 and tumor necrosis factor (TNF) may also augment IFN-gamma synthesis. We have investigated the relative contributions of these cytokines in the production of IFN-gamma and TNF by the Gram-positive bacterium Staphylococcus epidermidis, using the specific cytokine inhibitors IL-18 binding protein (IL-18BP), IL-1 receptor antagonist (IL-1Ra), anti-IL-12 antibodies (anti-IL-12 Ab), and TNF binding protein. Inhibition of caspase-1 reduced IFN-gamma and IL-1beta levels (by 80 and 67%, respectively) when heat-killed S. epidermidis was added to whole human blood cultures. IL-18BP reduced S. epidermidis-induced IFN-gamma (77% maximal suppression). In contrast, blocking IL-1 receptors by IL-1Ra had no effect on IFN-gamma production. Blocking endogenous IL-12 and TNF reduced IFN-gamma production by 69 and 36%. S. epidermidis-induced TNF-alpha was inhibited by IL-18BP and IL-1Ra, but not anti-IL-12 Ab, whereas IL-8 production was unaffected by any of the specific cytokine blocking agents. In conclusion, S. epidermidis stimulates IFN-gamma which is IL-18, IL-12 and TNF-dependent, but IL-1 independent.

Adult↗

PubMed2003

A surface amebic cysteine proteinase inactivates interleukin-18.

Amebiasis is a major cause of morbidity and mortality worldwide. Invasion by Entamoeba histolytica trophozoites causes secretion of proinflammatory cytokines from host epithelial cells, leading to a local acute inflammatory response, followed by lysis of colonic cells. Extracellular cysteine proteinases from amebic trophozoites are key virulence factors and have a number of important interactions with host defenses, including cleavage of immunoglobulin G (IgG), IgA, and complement components C3 and C5. Amebic lysates have also been shown to activate the precursor to interleukin 1-beta (proIL-1beta), mimicking the action of caspase-1. IL-18 is also a central cytokine, which induces gamma interferon (IFN-gamma) and activates macrophages, one of the main host defenses against invading trophozoites. Because proIL-18 is also activated by caspase-1, we evaluated whether amebic proteinases had a similar effect. Instead, we found that recombinant proIL-18 was cleaved into smaller fragments by the complex of surface-associated and released amebic proteinases. To evaluate the function of an individual proteinase from the complex pool, we expressed an active surface proteinase, EhCP5, which is functional only in E. histolytica. Recombinant EhCP5 expressed in Pichia pastoris had kinetic properties similar to those of the native enzyme with respect to substrate specificity and sensitivity to proteinase inhibitors. In contrast to the activation of proIL-1beta by amebic lysates, the purified proteinase cleaved proIL-18 and mature IL-18 to biologically inactive fragments. These studies suggest that the acute host response and amebic invasion result from a complex interplay of parasite virulence factors and host defenses. E. histolytica may block the host inflammatory response by a novel mechanism, inactivation of IL-18.

Amino Acid Sequence↗

PubMed2003

Effect of haemoperfusion on plasma paraquat concentration in vitro and in vivo.

This study was to observe the paraquat (PQ) reduction rate after haemoperfusion (HP) on the groups of a relatively large number: 50 survivors out of 105 patients with acute PQ poisoning. We started off by measuring the clearance of haemodialysis (HD) and HP for the PQ in vitro. At the blood flow of 250 mL/min, the PQ clearance was greater in HP than in HD during the first 90 minutes: 215 versus 175 mL/min at 30 minutes, 213 versus 201 mL/min at 60 minutes, and 199 versus 179 mL/min at 90 minutes. The clearance in HP decreased rapidly after two hours. By the end of the dialysis, however, the final concentration in container decreased to 5.7 microg/mL in HD and 1.5 microg/mL in HP, which implied that although HD was cleared more effectively during the later stages, the overall elimination was greater in HP. Following this preliminary investigation, we performed HP on all the patients in order to assess the extracorporeal elimination. One hundred and five patients who had swallowed one to three mouthfuls of PQ (24.5% w/v) solution were subjected to the in vivo study. The reduction rate of PQ was checked out by measuring the PQ concentration in plasma before and after four hours of HP. Seeing the reduction rate was significantly higher in the survivors group than in the nonsurvivors group (80.3+/-19.9 versus 67.2+/-19.2%, P <0.01), we concluded that adequate HP appears to be an indispensable treatment for patients with acute PQ poisoning.

Adult↗

PubMed2003

Mutation scan of a type 1 diabetes candidate gene: the human interleukin-18 binding protein gene.

Type 1 (insulin-dependent) diabetes, T1DM, is the result of an immune-mediated destruction of the pancreatic beta cells dependent mainly on T helper cells and macrophages. Interleukin-18 (IL-18) is a proinflammatory cytokine produced mainly by macrophages. IL-18 is capable of inducing T lymphocyte synthesis of IFNgamma, thereby skewing the T helper response toward a T helper type 1 (Th1) profile. IL-18 binding protein (IL18BP) neutralizes IL-18 and leads to a reduced Th1 response. Polymorphisms in IL18BP may affect the activity of IL-18 and the magnitude of the Th1 response and may play a role in the pathogenesis of T1DM. The aim of the study was therefore to identify polymorphisms in IL18BP and to test these for association with T1DM. We evaluated the human IL18BP gene on chromosome 11q13 as a candidate susceptibility gene for T1DM and scanned the entire IL18BP (promoter, exons 1-6, and 3'UTR) for polymorphisms using single-strand conformational polymorphism analysis and direct sequencing. We identified a total of 11 polymorphisms, all having allele frequencies ranging between 0.05 and 0.10. Four were in the 5'UTR: -257G-->T, -78C-->T, -65G-->A, and -59A-->G. Three were in intron 3: IVS3+140A-->C, IVS4-147G-->T, and IVS4-59G-->T. The last four, 38*A-->T, 48*T-->A, 388*C-->G, and 440*_441*insG, were in the 3'UTR of IL18BP. However, none of these were frequent enough to permit association studies in T1DM and we conclude that IL18BP does not contribute to the overall genetic susceptibility to type 1 diabetes.

Base Sequence↗

PubMed2002

Absence of p16INK4a and truncation of ARF tumor suppressors in chickens.

The INK4b-ARF-INK4a locus on human chromosome 9p21 (Human Genome Organization designation CDKN2B-CDKN2A), and the corresponding locus on mouse chromosome 4, encodes three distinct products: two members of the INK4 cyclin-dependent kinase inhibitor family and a completely unrelated protein, ARF, whose carboxyl-terminal half is specified by the second exon of INK4a but in an alternative reading frame. As INK4 proteins block the phosphorylation of the retinoblastoma gene product and ARF protects p53 from degradation, the locus plays a key role in tumor suppression and the control of cell proliferation. To gain further insights into the relative importance of INK4a and ARF in different settings, we have isolated and characterized the equivalent locus in chickens. Surprisingly, although we identified orthologues of INK4b and ARF, chickens do not encode an equivalent of INK4a. Moreover, the reading frame for chicken ARF does not extend into exon 2, because splicing occurs in a different register to that used in mammals. The resultant 60-aa product nevertheless shares functional attributes with its mammalian counterparts. As well as indicating that the locus has been subject to dynamic evolutionary pressures, these unexpected findings suggest that in chickens, the tumor-suppressor functions of INK4a have been compensated for by other genes.

Amino Acid Sequence↗

PubMed2002

Purification and characterization of a collagenase from the mackerel, Scomber japonicus.

Collagenase from the internal organs of a mackerel was purified using acetone precipitation, ion-exchange chromatography on a DEAE-Sephadex A-50, gel filtration chromatography on a Sephadex G-100, ion-exchange chromatography on DEAE-Sephacel, and gel filtration chromatography on a Sephadex G-75 column. The molecular mass of the purified enzyme was estimated to be 14.8 kDa by gel filtration and SDS-PAGE. The purification and yield were 39.5-fold and 0.1% when compared to those in the starting-crude extract. The optimum pH and temperature for the enzyme activity were around pH 7.5 and 55 degrees, respectively. The K(m) and V(max) of the enzyme for collagen Type I were approximately 1.1mM and 2,343 U, respectively. The purified enzyme was strongly inhibited by Hg2+, Zn2+, PMSF, TLCK, and the soybean-trypsin inhibitor.

Acetone↗

PubMed2002

A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity.

IL-1F7 was discovered in expressed sequence tag databases as a member of the increasing family of proteins sharing sequence homology to IL-1alpha/beta, IL-1Ra, and IL-18. In the present study using immunohistochemical staining, IL-1F7 was localized in human peripheral monocytic cells, suggesting its role in immune regulation. Recombinant human IL-1F7b was shown to bind to the IL-18Ralpha but without IL-18 agonistic or antagonistic function. Using chemical cross-linking, we observed that, unlike IL-18, IL-1F7b fails to recruit the IL-18Rbeta chain to form a functionally active, ternary complex with the IL-18Ralpha chain. IL-1F7b shares two conserved amino acids with IL-18 (Glu-35 and Lys-124), which participate in the interaction of IL-18 with the IL-18Ralpha chain as well as the IL-18-binding protein (IL-18BP), a secreted protein that neutralizes IL-18 activity. 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. This effect was observed primarily at limiting concentrations of IL-18BP (3.12-12.5 ng/ml) and at a 50- to 100-fold molar excess of IL-1F7b. Similar results were obtained by using isolated human peripheral blood mononuclear cells. To study the molecular basis of this effect we performed binding studies of IL-1F7b and IL-18BP. After cross-linking, a high molecular weight complex consisting of IL-1F7b and IL-18BP was observed on SDS/PAGE. We propose that after binding to IL-18BP, IL-1F7b forms a complex with IL-18Rbeta, depriving the beta-chain of forming a functional receptor complex with IL-18Ralpha and thus inhibiting IL-18 activity.

Amino Acid Sequence↗

PubMed2002

Differential gene regulation by specific gain-of-function JNK1 proteins expressed in Swiss 3T3 fibroblasts.

The c-Jun N-terminal kinases (JNKs) are encoded by three genes that yield 10 isoforms through alternative mRNA splicing. The roles of each JNK isoform in the many putative biological responses where the JNK pathway is activated are still unclear. To examine the cellular responses mediated by different JNK isoforms, gain-of-function JNK1 polypeptides were generated by fusing the upstream mitogen-activated protein kinase kinase, MKK7, with p46JNK1alpha or p46JNK1beta. The MKK7-JNK fusion proteins, which exhibited constitutive activity in 293T cells, were stably expressed in Swiss 3T3 fibroblasts using retrovirus-mediated gene transfer. Swiss 3T3 cells expressing either of the MKK7-JNK polypeptides were equally sensitized to induction of cell death following serum withdrawal. To search for other cellular responses that may be selectively regulated by the JNK1 isoforms, the gene expression profiles of Swiss 3T3 cells expressing MKK7-JNK1alpha or MKK7-JNK1beta were compared with empty vector-transfected control cells. Affymetrix Genechips identified 46 genes for which expression was increased in MKK7-JNK-expressing cells relative to vector control cells. Twenty genes including those for c-Jun, MKP-7, interluekin-1 receptor family member ST2L/ST2, and c-Jun-binding protein were induced similarly by MKK7-JNK1alpha and MKK7-JNK1beta proteins, whereas 13 genes were selectively increased by MKK7-JNK1alpha and 13 genes were selectively increased by MKK7-JNK1beta. The set of genes selectively induced by MKK7-JNK1beta included a number of known interferon-stimulated genes (ISG12, ISG15, IGTP, and GTPI). Consistent with these gene expression changes, Swiss 3T3 cells expressing MKK7-JNK1beta exhibited increased resistance to vesicular stomatitis virus-induced cell death. These findings reveal evidence for JNK isoform-selective gene regulation and support a role for distinct JNK isoforms in specific cellular responses.

3T3 Cells↗

PubMed2002

IL-18-binding protein expression by endothelial cells and macrophages is up-regulated during active Crohn's disease.

The pathogenesis of Crohn's disease (CD) remains under intense investigation. Increasing evidence suggests a role for mature IL-18 in the induction of proinflammatory cytokines and Th1 polarization in CD lesions. The aim of this study was to investigate the contribution of the IL-18-neutralizing (a and c) and non-neutralizing (b and d) isoforms of IL-18-binding protein (IL-18BP) during active CD. Intestinal endothelial cells and macrophages were the major source of IL-18BP within the submucosa, and this IL-18BP production was also found to be relevant to other types of endothelial cells (HUVEC) and macrophages (peripheral monocytes). IL-18BP messenger transcript and protein were significantly increased in surgically resected specimens from active CD compared with control patients, correlating with an up-regulation of IL-18. Analysis of the expression of the four IL-18BP isoforms as well as being free or bound to IL-18 was reported and revealed that unbound IL-18BP isoforms a and c and inactive isoform d were present in specimens from active CD and control patients while isoform b was not detected. IL-18/IL-18BP complex was also detected. Interestingly, although most was complexed, free mature IL-18 could still be detected in active CD specimens even in the presence of the IL-18BP isoform a/c. These results demonstrate that the appropriate neutralizing isoforms are present in the intestinal tissue of patients with active CD and highlights the complexity of IL-18/IL-18BP biology.

Adult↗

PubMed2002

The role of endogenous interleukin (IL)-18, IL-12, IL-1beta, and tumor necrosis factor-alpha in the production of interferon-gamma induced by Candida albicans in human whole-blood cultures.

Despite the importance of interferon (IFN)-gamma, tumor necrosis factor (TNF), and interleukin (IL)-18 for host defense against candidiasis, the pathways leading to their stimulation by Candida albicans are unclear. In a whole-blood model, IL-18 neutralization by IL-18 binding protein decreased C. albicans-induced IFN-gamma synthesis by 72%. Similarly, neutralization of IL-12 or IL-1beta by either neutralizing antibodies or IL-1 receptor antagonist also reduced (by 65%) IFN-gamma production. Neutralization of TNF by TNF binding proteins resulted in only a 36% reduction of IFN-gamma synthesis. In contrast, production of TNF and IL-8 was largely unaffected by these cytokine inhibitors. Thus, C. albicans stimulates IFN-gamma production in an IL-18-, IL-12-, and IL-1beta-dependent manner, whereas production of TNF and IL-8 is independent of these cytokines. Blocking the biologic activities of IL-18, IL-12, and IL-1beta in patients (e.g., for treatment of autoimmune diseases) may result in increased susceptibility to C. albicans infection.

Adult↗

PubMed2002

The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines.

Suberoylanilide hydroxamic acid (SAHA) is a hydroxamic acid-containing hybrid polar molecule; SAHA specifically binds to and inhibits the activity of histone deacetylase. Although SAHA, like other inhibitors of histone deacetylase, exhibits antitumor effects by increasing expression of genes regulating tumor survival, we found that SAHA reduces the production of proinflammatory cytokines in vivo and in vitro. A single oral administration of SAHA to mice dose-dependently reduced circulating TNF-alpha, IL-1-beta, IL-6, and IFN-gamma induced by lipopolysaccharide (LPS). Administration of SAHA also reduced hepatic cellular injury in mice following i.v. injection of Con A. SAHA inhibited nitric oxide release in mouse macrophages stimulated by the combination of TNF-alpha plus IFN-gamma. Human peripheral blood mononuclear cells stimulated with LPS in the presence of SAHA released less TNF-alpha, IL-1-beta, IL-12, and IFN-gamma (50% reduction at 100-200 nM). The production of IFN-gamma stimulated by IL-18 plus IL-12 was also inhibited by SAHA (85% at 200 nM). However, SAHA did not affect LPS-induced synthesis of the IL-1-beta precursor, the IL-1 receptor antagonist, or the chemokine IL-8. In addition, IFN-gamma induced by anti-CD3 was not suppressed by SAHA. Steady-state mRNA levels for LPS-induced TNF-alpha and IFN-gamma in peripheral blood mononuclear cells were markedly decreased, whereas IL-8 and IL-1-beta mRNA levels were unaffected. Because SAHA exhibits antiinflammatory properties in vivo and in vitro, inhibitors of histone deacetylase may stimulate the expression of genes that control the synthesis of cytokines and nitric oxide or hyperacetylate other targets.

Animals↗

PubMed2002

Identification of amino acid residues critical for biological activity in human interleukin-18.

Interleukin-18 (IL-18) is a pro-inflammatory cytokine, and IL-18-binding protein (IL-18BP) is a naturally occurring protein that binds IL-18 and neutralizes its biological activities. Computer modeling of human IL-18 identified two charged residues, Glu-42 and Lys-89, which interact with oppositely charged amino acid residues buried in a large hydrophobic pocket of IL-18BP. The cell surface IL-18 receptor alpha chain competes with IL-18BP for IL-18 binding, although the IL-18 receptor alpha chain does not share significant homology to IL-18BP. In the present study, Glu-42 was mutated to Lys and Lys-89 to Glu; Glu-42 and Lys-89 were also deleted separately. The deletion mutants (E42X and K89X) were devoid of biological activity, and the K89E mutant lost 95% of its activity. In contrast, compared with wild-type (WT) IL-18, the E42K mutant exhibited a 2-fold increase in biological activity and required a 4-fold greater concentration of IL-18BP for neutralization. The binding of WT IL-18 and its various mutants to human natural killer cells was evaluated by competition assays. The mutant E42K was more effective than WT IL-18 in inhibiting the binding of (125)I-IL-18 to natural killer cells, whereas the three inactive mutants E42X, K89E, and K89X were unable to compete with (125)I-IL-18 for binding. Similarly, WT IL-18 and the E42K mutant induced degradation of Ikappa-Balpha, whereas the three biologically inactive mutants did not induce degradation. The present study reveals that Glu-42 and Lys-89 are critical amino acid residues for the integrity of IL-18 structure and are important for binding to cell surface receptors, for signal transduction, and for neutralization by IL-18BP.

Amino Acid Sequence↗

PubMed2002

The combination of soluble IL-18Ralpha and IL-18Rbeta chains inhibits IL-18-induced IFN-gamma.

Although the beta chain of interleukin-18 receptor (IL-18Rbeta) is required for signaling, the soluble (extracellular) form does not bind IL-18, and its role in inhibiting IL-18 is unclear. In the present study, both the soluble human IL-18 ligand binding alpha chain (sIL-18Ralpha) and the sIL-18Rbeta chain were investigated for inhibition of IL-18-induced interferon-gamma (IFN-gamma) production in human peripheral blood mononuclear cells (PBMC), whole blood, and KG-1 macrophage and natural killer (NK) cell lines. Neutralization of IL-18 by soluble receptors was compared with that of the IL-18 binding protein (IL-18BP). An equimolar concentration IL-18BP inhibited 90% of IL-18 activity, whereas a 4-fold molar excess of sIL-18Ralpha had no effect. A dimeric construct of sIL-18Ralpha linked to the Fc domain of IgG1 (sIL-18Ralpha:Fc) increased IL-18 activity 2.5-fold. In PBMC stimulated with lypopolysaccharide (LPS) or in whole blood stimulated with Staphylococcus epidermidis, 3 nM IL-18BP reduced IFN-gamma by 80%, whereas IL-18Ralpha:Fc had no effect. A construct of the sIL-18Rbeta linked to Fc (sIL-18Rbeta:Fc) did not affect IL-18-induced IFN-gamma even at 80-fold molar excess of IL-18. However, the combination of both soluble receptors reduced IFN-gamma by 80%. In KG-1 cells, a 50% reduction in IL-18 activity was observed using an 80-fold molar excess of sIL-18Ralpha:Fc but only in the presence of sIL-18Rbeta:Fc. Similarly, a 50% reduction was observed using sIL-18Rbeta:Fc in the presence of a molar excess of sIL-18Ralpha:Fc. Similar inhibition was observed in NK cells. These studies reveal that the combination of the ligand-binding and the nonligand-binding extracellular domains of IL-18R is needed to inhibit IL-18, whereas IL-18BP neutralizes at equimolar concentration.

Adult↗

PubMed2002

Rat interleukin-18 binding protein: cloning, expression, and characterization.

Interleukin-18 binding protein (IL-18BP) is a constitutively expressed and secreted protein that lacks a transmembrane domain. IL-18BP binds specifically to mature IL-18 and inhibits its activity. To study the immunomodulating role of IL-18BP in models of autoimmune diseases in rats, we cloned and characterized rat IL-18BP. Rat IL-18BP has 193 amino acid residues and is highly homologous to human and mouse IL-18BP. Recombinant rat IL-18BP binds to rat IL-18, reacts with antibodies to human or mouse IL-18BP, and inhibits IL-18-dependent interferon-gamma (IFN-gamma) production in vitro. Thus, rat IL-18BP can be employed to antagonize the proinflammatory responses induced by endogenous IL-18 in rat models of autoimmune diseases.

Amino Acid Sequence↗