Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial infection results in the production of inflammatory mediators and may be involved in the pathogenesis of sepsis and/or systemic inflammatory response syndrome. The effect of lipopolysaccharide (LPS), a major component of the outer surface of Gram-negative bacteria, and Staphylococcal enterotoxin B (SEB), a superantigen of Gram-positive bacteria, on cytokine production in peripheral blood mononuclear cells (PBMCs) was examined. LPS significantly increased the production of proinflammatory and anti-inflammatory cytokines, and SEB enhanced the production of helper T lymphocyte type cytokines. These results illustrated the different responses to Gram-negative and Gram-positive bacterial infections. The effect of gabexate mesilate, a synthetic protease inhibitor, on cytokine production and expression of the toll-like receptor (TLR) was also examined. The results suggest that gabexate mesilate-induced inhibition of tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18) production in LPS-stimulated PBMCs is due to the inhibition of the nuclear factor-kappa B activation pathway and/or inhibition of the processing pathway of pro-TNF-alpha and pro-IL-18, not to down-regulation of TLR-2 or TLR-4.
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PMID:Differential cytokine response in host defence mechanisms triggered by gram-negative and gram-positive bacteria, and the roles of gabexate mesilate, a synthetic protease inhibitor. 1202 32

The innate immune system uses a variety of germline-encoded pattern-recognition receptors that recognize conserved microbial structures or pathogen-associated molecular patterns, such as those that occur in the bacterial cell-wall components peptidoglycan and lipopolysaccharide. Recent studies have highlighted the importance of Toll-like receptors (TLRs) as a family of pattern-recognition receptors in mammals that can discriminate between chemically diverse classes of microbial products. First identified on the basis of sequence similarity with the Drosophila protein Toll, TLRs are members of an ancient superfamily of proteins, which includes related proteins in invertebrates and plants. TLRs activate innate immune defense reactions, such as the release of inflammatory cytokines, but increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The sequence similarity between the intracellular domains of the TLRs and the mammalian interleukin-1 and interleukin-18 cytokine receptors reflects the use of a common intracellular signal-transduction cascade triggered by these receptor classes. But more recent findings have demonstrated that there are in fact TLR-specific signaling pathways and cellular responses. Thus, TLRs function as sentinels of the mammalian immune system that can discriminate between diverse pathogen-associated molecular patterns and then elicit pathogen-specific cellular immune responses.
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PMID:Toll-like receptors: a family of pattern-recognition receptors in mammals. 1218 54

In this study, we investigated the expression of interleukin-18 (IL-18) in porcine airway and intestinal epithelium. We found constitutive protein expression of precursor IL-18 in primary culture of porcine airway epithelium. Immunohistochemical staining revealed that porcine IL-18 was localized in the porcine airway epithelium and that it was significantly upregulated with experimental endotoxemia induced by Escherichia coli lipopolysaccharide (LPS) inoculation. We also confirmed by immunohistochemical staining that IL-18 was expressed in porcine intestinal epithelial cells. Moreover, the concentration of IL-18 in intestinal cell lysates of 1-day-old piglets was about 3-fold and 6-fold less than that in those of 1-month-old and 6-month-old piglets, respectively. Exogenous IL-18 was able to induce interferon-gamma (IFN-gamma) in the peripheral blood of 1-day-old piglets, whereas concanavalin A (ConA) was not able to induce IFN-gamma in the same condition. These results suggest that mucosal epithelial cells are among the major sources of IL-18 in pig and that IL-18 may be useful as a therapeutic agent for the enhancement of immune responses and as a vaccine adjuvant, especially in neonatal piglets.
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PMID:Expression of interleukin-18 by porcine airway and intestinal epithelium. 1239 28

Sepsis is thought to result from an exaggerated innate immune response to microbial components such as lipopolysaccharide (LPS), but the involvement of a specific mechanism(s) has not been identified. We studied the role of caspase 1 (Cas-1) in the murine innate immune response to infection with gram-negative bacteria and to nonlethal and lethal doses of LPS. cas-1(-/-) and Cas-1 inhibitor (Ac-YVAD-CHO)-treated cas-1(+/+) mice were two- to threefold more susceptible to lethal Escherichia coli infection than cas-1(+/+) mice. Administration of Cas-1 products, interleukin-18 (IL-18) or IL-1beta, protected three of three and six of seven mice, respectively, from lethal infection with E. coli compared to none of six of untreated mice (P = 0.0082). Therefore, cas-1 is essential for antibacterial host defense. Nonlethal (75 micro g) and lethal (500 micro g) doses of LPS induce different patterns of gamma interferon, IL-1beta, and IL-18 expression. Consequently, the role of Cas-1, which cleaves pro-IL-18 and pro-IL-1beta to their active forms, was investigated in these disparate conditions by using enzymatic assay and reverse transcription-PCR. At 75 micro g, LPS induced a transient increase in IL-1beta and IL-18 levels in serum, whereas at 500 micro g it induced a 1.5-fold-higher IL-18 level in serum, which increased till death. At 75 micro g of LPS, splenic cas-1 mRNA expression remained unchanged at all time points, but activity increased transiently at 3 h. In lethally treated mice, Cas-1 activity remained elevated until death; however, cas-1 mRNA levels increased at 3 h and decreased to basal levels by 8 h. Treatment with Cas-1 inhibitor protected mice from lethal endotoxemia. Thus, Cas-1 is essential for innate antibacterial host defenses and may represent a mechanism of innate immunity that upon excessive stimulation by microbial components may lead to endotoxic shock.
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PMID:Role of caspase 1 in murine antibacterial host defenses and lethal endotoxemia. 1243 67

Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans. Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses. Since oral epithelial cells secrete a variety of cytokines and chemokines in response to oral microorganisms and since C. albicans is closely associated with oral epithelial cells as a commensal organism, we wanted to determine whether interleukin-18 (IL-18) and gamma interferon (IFN-gamma) were produced by oral epithelial cells in response to C. albicans infection and lipopolysaccharide (LPS) stimulation. Our results showed that IL-18 mRNA and protein were constitutively expressed by oral epithelial cells and were down-regulated by Candida infections but increased following LPS stimulation. Both C. albicans and LPS significantly decreased pro-IL-18 (24 kDa) levels and increased active IL-18 (18 kDa) levels. This effect was IL-1beta-converting-enzyme dependent. The increase in active IL-18 protein levels promoted the production of IFN-gamma by infected cells. No effect was obtained with LPS. Although produced only at an early stage, secreted IFN-gamma seemed to be a preferential response by oral epithelial cells to C. albicans growth. These results provide additional evidence for the contribution of oral epithelial cells to local (direct contact) and systemic (IL-18 and IFN-gamma production) defense against exogenous stimulation such as C. albicans infection or LPS stimulation.
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PMID:Interleukin-18 and gamma interferon production by oral epithelial cells in response to exposure to Candida albicans or lipopolysaccharide stimulation. 1243 88

Originally identified as the gamma interferon-inducing factor, interleukin-18 (IL-18) was rediscovered as a proinflammatory cytokine related to the IL-1 family of cytokines that plays an important role in both innate and adaptive immune responses against viruses and intracellular pathogens. Despite its importance in inducing and regulating immune responses, relatively little is known about its production in HIV infection. We report here significantly (P < 0.05) elevated levels of this cytokine in the sera of human immunodeficiency virus (HIV)-infected/AIDS patients compared to those of HIV-seronegative healthy persons. Surprisingly, the peripheral blood mononuclear cells (PBMC) from HIV-infected/AIDS patients were compromised in the ability to upregulate IL-18 gene expression and produce this cytokine with and without lipopolysaccharide (LPS) stimulation. A significant positive correlation (P < 0.05) existed between the concentration of IL-18 in serum and its production from PBMC of HIV-seronegative healthy individuals but not those of HIV-infected/AIDS patients. Furthermore, the patients' PBMC expressed relatively reduced levels of activated caspase-1 constitutively as well as in response to LPS stimulation. Our data suggest the involvement of transforming growth factor beta (TGF-beta) in suppressing IL-18 production from the patients' PBMC for the following reasons. (i) In in vitro studies it suppressed the production of IL-18 from PBMC. (ii) Its levels were significantly higher in the plasma of patients compared to that of control subjects. (iii) A significant negative correlation existed between the concentrations of TGF-beta in plasma and of IL-18 in serum of the patients. The elevated levels of IL-18 in the serum of HIV-infected individuals may contribute to AIDS pathogenesis, whereas its compromised production from their PBMC in response to stimuli may reduce their innate defense to opportunistic intracellular pathogens.
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PMID:Elevated levels of circulating interleukin-18 in human immunodeficiency virus-infected individuals: role of peripheral blood mononuclear cells and implications for AIDS pathogenesis. 1243 70

Epithelial cells play a critical role in periodontal disease through the secretion of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18). However, the role played by fibroblasts is still unclear. The rationale of this study was to throw light on the role of gingival fibroblasts in periodontal disease. We thus investigated the expression of IL-1 beta, IL-18, and ICE mRNA and the secretion of the corresponding proteins by human normal gingival fibroblasts before and after stimulation with lipopolysaccharide (LPS) from Porphyromonas gingivalis and Escherichia coli. IL-1 beta, IL-18, and ICE mRNA expression was evaluated by RT-PCR. Proteins were analyzed by Western blot and ELISA. We demonstrated that gingival fibroblasts expressed ICE mRNA. Basal expression of ICE was modulated following cell stimulation with lipopolysaccharide (5 mug/ml). However, gingival fibroblasts expressed low levels of IL-1 beta mRNA. The expression was potentiated by LPS. The expression of IL-1 beta mRNA was followed by the secretion of IL-1 beta but not IL-18 protein. Our study suggests that fibroblasts may be involved in the defense against infections via an IL-1 beta-mediated but not an IL-18-mediated mechanism.
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PMID:Gingival and dermal fibroblasts produce interleukin-1 beta converting enzyme and interleukin-1 beta but not interleukin-18 even after stimulation with lipopolysaccharide. 1458 52

Induction of expression of adhesion molecules is a crucial step in inflammation. The role of interleukin-18 (IL-18) in induction of various adhesion molecules was investigated in freshly isolated peripheral blood mononuclear cells and human monocyte and T-cell lines. IL-18 selectively up-regulated intercellular adhesion molecule-1 (ICAM-1) expression on freshly isolated human monocytes, but not on lymphocytes. The expression of other adhesion molecules was not influenced. Induction of ICAM-1 by IL-18 was dependent on endogenous tumour necrosis factor-alpha (TNF-alpha), and IL-12 had an additive effect on that of IL-18. No changes in adhesion molecule expression were observed on the monocytic cell line THP-1 and on the T-cell lines HSB-2 and Jurkat J16. In addition, induction of ICAM-1 on monocytes by lipopolysaccharide was slightly, but significantly, inhibited by blockade of either endogenous IL-18 or TNF-alpha with IL-18 binding protein or TNF binding protein, respectively. Blocking IL-1 effects with IL-1 receptor antagonist did not influence ICAM-1 levels. In conclusion, IL-18 selectively up-regulates the expression of ICAM-1 on monocytes, and this contributes to the proinflammatory effects of this cytokine.
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PMID:Selective regulation of intercellular adhesion molecule-1 expression by interleukin-18 and interleukin-12 on human monocytes. 1463 60

Monocytes release interleukin-18 after activation by lipopolysaccharide/ATP. Since inflammatory conditions such as sepsis are characterized by augmented interleukin-18 in sera of patients, we sought to modulate lipopolysaccharide/ATP-induced interleukin-18 release by pharmacological means. Here we report that 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), an inhibitor of ATP-mediated cellular activation by the purinoreceptor subtype P(2x7), potently suppresses interleukin-18 release from peripheral blood mononuclear cells. Interleukin-18 liberation was likewise inhibited by glyburide, a modulator of ion transport and inhibitor of ATP-binding cassette transporter 1. The data presented herein indicate that by pharmacologically interfering with the process of cytokine secretion agents such as KN-62 or glyburide have the potential to curb overproduction of interleukin-18 in septic patients.
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PMID:Inhibition of lipopolysaccharide/ATP-induced release of interleukin-18 by KN-62 and glyburide. 1466 39

The purpose of this present study was to explore the therapeutic potential of prostaglandins E1 and E2 on the systemic inflammatory response evoked by endotoxin. Since interleukin-18, a monocyte-derived cytokine, is increased during sepsis, decreasing the production of interleukin-18 is important in treating this condition. Prostaglandin E1 and E2 inhibited interleukin-18 production in human monocytes treated with lipopolysaccharide and prostanoid IP-, EP2- and EP4-receptor agonists mimicked the effects of prostaglandins E1 and E2. Therefore, prostanoid IP, EP2- and EP4-receptors might be involved in the decrease in interleukin-18 production during sepsis.
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PMID:Prostaglandins E1 and E2 inhibit lipopolysaccharide-induced interleukin-18 production in monocytes. 1598 61


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