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)

Repeated intratracheal instillations of E. coli lipopolysaccharide (LPS) in hamster lungs cause an influx of polymorphonuclear leukocytes (PMNs) into the alveolar walls, with concomitant development of severe emphysema. It has been suggested that elastase, released by these PMNs, is involved in the development of emphysema. This study demonstrates the release of elastase from recruited PMNs in cryostat sections of hamster lungs, after being treated once, twice, or thrice with LPS, intratracheally. Elastase activity was visualized using two elastase-specific synthetic substrates, to which a methoxynaphthylamine (MNA) group had been bound covalently. Liberated MNA, when made insoluble by coupling with 5-nitrosalicylaldehyde, fluoresces strongly. The authors observed that the interval between start of incubation and appearance of fluorescence and the intensity of fluorescence correlated with the number of LPS administrations. Fluorescence was observed to be located in or in close vicinity to alveolar walls. No fluorescence was observed in sections of untreated hamsters. Liberation of MNA from synthetic substrates was delayed strongly by the addition of a recombinant secretory leukocyte proteinase inhibitor or a substituted cephalosporin neutrophil elastase inhibitor. The authors conclude that LPS-mediated PMN influx into the lung is accompanied by release of elastase from these cells and speculate that this PMN-elastase is involved in the development of LPS-mediated emphysema.
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PMID:Detection of extracellular neutrophil elastase in hamster lungs after intratracheal instillation of E. coli lipopolysaccharide using a fluorogenic, elastase-specific, synthetic substrate. 163 60

Secretory leukocyte protease inhibitor (SLPI) is a potent proteinase inhibitor produced in the lung. Stimulated neutrophils at sites of inflammation can inactivate SLPI by myeloperoxidase-mediated oxidation of the methionine residue in the active site of SLPI. Apocynin is a selective inhibitor of NADPH oxidase and may therefore protect SLPI against neutrophil-mediated oxidative inactivation. The aim of the present study was to determine the effect of apocynin on the efficacy of SLPI in preventing experimental emphysema. To investigate the effect of apocynin on emphysema without SLPI treatment, three groups of eight hamsters each received drinking water containing apocynin at concentrations of 2, 20, and 200 micrograms/ml, respectively. Emphysema was induced in these hamsters by intratracheal instillations of 500 micrograms of lipopolysaccharide (LPS) twice a week for 4 wk. In hamsters that received 200 micrograms/ml apocynin, the development of emphysema was reduced by 26.2% (p = 0.01). Other apocynin concentrations had no effect. The experiment was repeated, with SLPI added to the treatment. Of a total of six groups of hamsters, four groups (three with apocynin and one with solvent) received twice-weekly doses of a mixture of 500 micrograms of LPS and 1 mg SLPI in 200 microliters saline in the trachea for 4 wk. In addition, each LPS instillation was followed 24 and 48 h later by an instillation containing 1 mg of SLPI. Apocynin (20 and 200 micrograms/ml) improved the protective effect of SLPI from 37 to 64% and 79%, respectively (p < 0.01). We conclude that oral administration of apocynin can improve the efficacy of SLPI in preventing LPS-induced emphysema.
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PMID:Apocynin improves the efficacy of secretory leukocyte protease inhibitor in experimental emphysema. 795 25

Experiments were performed to test whether recombinant secretory leukocyte proteinase inhibitor (rSLPI) was able to prevent the development of lipopolysaccharide (LPS)-mediated pulmonary emphysema, hemorrhage, and secretory cell metaplasia (SCM) in hamsters. Several groups of eight animals were intratracheally treated for four weeks, twice a week with 0.5 mg Escherichia coli LPS or with saline. In the first experiment, an additional group of eight hamsters was treated with 0.5 mg LPS mixed with 0.5 mg rSLPI, and the animals received another instillation of 0.5 mg rSLPI 7 h later. In the second experiment, 0.5 mg LPS, mixed with 1 mg rSLPI, was given while additional instillations of 1 mg rSLPI were performed 7 h and 31 h after the first dosage. In the third experiment, 0.5 mg LPS, mixed with 0.5, 1.5, or 3.0 mg rSLPI, was given while additional instillations of 0.5, 1.5, and 3.0 mg rSLPI, respectively, were performed 24 h and 48 h after the first dosage. Hamster lungs were examined for emphysema, hemorrhage, and SCM. In all three series of experiments, we observed a significant inhibition of LPS-mediated emphysema by rSLPI. This inhibition tended to be dose related. Inconclusive results were obtained on the inhibition of LPS-mediated hemorrhage. The development of LPS-mediated SCM was not affected by rSLPI. The LPS-mediated polymorphonuclear leukocyte (PMN) influx did not change when administrations of rSLPI were given additionally. We conclude that rSLPI is able to diminish significantly the development of LPS-mediated pulmonary emphysema in hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of lipopolysaccharide-induced pulmonary emphysema by intratracheally instilled recombinant secretory leukocyte proteinase inhibitor. 809 78

Release and cellular contents of pro- and anti-inflammatory cytokines, neutrophilic elastase and secretory leukocyte proteinase inhibitor (SLPI) were measured with enzyme-linked immunosorbent assay in peripheral blood mono- and polymorphonuclear cells stimulated with preopsonized yeast cells or lipopolysaccharide. Tumour necrosis factor alpha (TNF alpha) was also measured with a bioassay. TNF alpha production and soluble TNF alpha receptor I (sTNF RI) were demonstrated in the environment of both cell populations. The bioassay indicated levels of TNF alpha far below those detected by ELISA. The overall secretion of cytokines and their inhibitors was found to favour an anti-inflammatory balance in the environment of the stimulated cells. The interleukin-1 receptor antagonist (IL1-ra), compared with interleukin-1 beta (IL-1 beta), dominated the secretions from both cell types with a 100- to 1000-fold excess respectively. Most of the translated IL-1 beta was not secreted but found associated with the cellular compartments. In contrast to lipopolysaccharide (LPS) stimulation, preopsonized yeast cells stimulated a massive release of elastase from neutrophil cells.
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PMID:Release of cytokines and proteases from human peripheral blood mononuclear and polymorphonuclear cells following phagocytosis and LPS stimulation. 886 69

To explore regulation of potentially lethal responses to bacterial lipopolysaccharide (LPS), we used differential display under LPS-free conditions to compare macrophage cell lines from two strains of mice congenic for a locus affecting LPS sensitivity. LPS-hyporesponsive cells, primary macrophages, and polymorphonuclear leukocytes transcribed secretory leukocyte protease inhibitor (SLPI), a known epithelial cell-derived inhibitor of leukocyte serine proteases. Transfection of macrophages with SLPI suppressed LPS-induced activation of NF-kappa B and production of nitric oxide and TNF alpha. The ability of interferon-gamma (IFN gamma) to restore LPS responsiveness is a hallmark of the LPS-hyporesponsive phenotype. IFN gamma suppressed expression of SLPI and restored LPS responsiveness to SLPI-producing cells. Thus, SLPI is an LPS-induced IFN gamma-suppressible phagocyte product that serves to inhibit LPS responses.
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PMID:Secretory leukocyte protease inhibitor: a macrophage product induced by and antagonistic to bacterial lipopolysaccharide. 903 68

Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.
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PMID:Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells. 942 67

Mouse secretory leukocyte protease inhibitor (SLPI) was recently characterized as a lipopolysaccharide (LPS)-induced product of macrophages that antagonizes their LPS-induced activation of NF-kappaB and production of NO and tumor necrosis factor (TNF) (F. Y. Jin, C. Nathan, D. Radzioch, and A. Ding, Cell 88:417-426, 1997). To better understand the role of SLPI in innate immune and inflammatory responses, we examined the kinetics of SLPI expression in response to LPS, LPS-induced cytokines, and LPS-mimetic compounds. SLPI mRNA was detectable in macrophages by Northern blot analysis within 30 min of exposure to LPS but levels peaked only at 24 to 36 h and remained elevated at 72 h. Despite the slowly mounting and prolonged response, early expression of SLPI mRNA was cycloheximide resistant. Two LPS-induced proteins-interleukin-10 (IL-10) and IL-6-also induced SLPI, while TNF and IL-1beta did not. The slow attainment of maximal induction of SLPI by LPS in vitro was mimicked by infection with Pseudomonas aeruginosa in vivo, where SLPI expression in the lung peaked at 3 days. Two LPS-mimetic molecules-taxol from yew bark and lipoteichoic acid (LTA) from gram-positive bacterial cell walls-also induced SLPI. Transfection of macrophages with SLPI inhibited their LTA-induced NO production. An anti-inflammatory role for macrophage-derived SLPI seems likely based on SLPI's slowly mounting production in response to constituents of gram-negative and gram-positive bacteria, its induction both as a direct response to LPS and as a response to anti-inflammatory cytokines induced by LPS, and its ability to suppress the production of proinflammatory products by macrophages stimulated with constituents of both gram-positive and gram-negative bacteria.
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PMID:Lipopolysaccharide-related stimuli induce expression of the secretory leukocyte protease inhibitor, a macrophage-derived lipopolysaccharide inhibitor. 959 1

To explore gene regulation by bacterial lipopolysaccharide (LPS), we compared mRNA profiles of macrophage cell lines from two strains of mice congenic for a locus markedly affecting their ability to respond to LPS. Differential display detected four differentially expressed transcripts. One transcript encoded the mouse homolog of human secretory leukocyte protease inhibitor (SLPI), which was expressed by LPS-hyporesponsive macrophage cells (Lps(d)) but not by LPS-normoresponsive cells (Lps(n)). Among five macrophage cell lines, secretion of SLPI was inversely correlated with ability to produce nitric oxide (NO) and tumor necrosis factor alpha in response to LPS. Stable transfection of LPS-responsive macrophages with SLPI suppressed LPS-induced responses. Interferon-gamma (IFN-gamma), which corrects the defective LPS response in Lps(d) macrophages, suppressed the LPS-induced expression of SLPI and restored LPS response to SLPI-overexpressing macrophages. Besides its role as a LPS response inhibitor, mouse SLPI is also a lipoteichoic acid response inhibitor. The expression of SLPI was strongly enhanced by interleukin-10 and -6. SLPI may be an important antiinflammatory molecule in host defense against gram-negative and gram-positive bacteria.
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PMID:Identification of genes involved in innate responsiveness to bacterial products by differential display. 1004 47

Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor abundantly found in mucous secretions of lung, is thought to serve as an important protective component in the secretory fluids at sites of degenerative and inflammatory diseases. In this study, we examined the effects of SLPI on the production of a proinflammatory cytokine, TNF-alpha, and immunosupressive cytokines, IL-10 and transforming growth factor-beta (TGF-beta) by macrophages (M phi s), in response to lipopolysaccharide (LPS)-mediated stimulation and M. avium complex (MAC) infection, using recombinant half-sized SLPI (1/2 SLPI) consisting of C-terminal domain (Arg55-Ala107) of intact SLPI. In addition, effects of SLPI on the production of nitric oxide radicals (NO), important antimicrobial effectors of M phi s against micro-organisms, by these M phi s were studied. First, when the number of TNF-alpha producing cells in the LPS-stimulated M phi population was counted by the ELISPOT assay, more than half of the M phi s acquired TNF-alpha secreting ability at 24 hr after LPS stimulation. On the other hand, MAC-infected M phi s produced detectable amounts of TNF-alpha into culture fluid during the first 24 hr. In both cases, 1/2 SLPI did not affect the LPS- or MAC-induced TNF-alpha production by M phi s. Second, when the production of IL-10 and TGF-beta by M phi s was determined by measuring the amounts of these cytokines accumulated in M phi culture fluids by ELISA, the following was observed. M phi IL-10 production was rapidly increased in the early phase of cultivation after LPS stimulation or MAC infection, peaking on day 1 and thereafter declining to normal level by day 14. Half-sized SLPI did not affect IL-10 production of LPS-stimulated M phi s, while it caused slight enhancement of IL-10 production by MAC-infected M phi s. M phi TGF-beta production was initiated in the middle phase (day 7) of M phi cultivation and continued until day 14. Notably, 1/2 SLPI markedly potentiated the TGF-beta producing ability of the LPS-stimulated M phi s. Moreover, 1/2 SLPI caused moderate increase in the TGF-beta production by MAC-infected M phi s. Third, significantly potentiated NO production was observed in M phi s during the first 2 days after LPS stimulation and MAC infection. Half-sized SLPI did not affect the NO production by LPS-stimulated or MAC-infected M phi s. These findings indicate that SLPI up-regulates the production of some immunoregulatory cytokines including IL-10 and TGF-beta, particularly the latter, by M phi s in response to LPS stimulation or MAC infection, thereby suggesting the possibility that SLPI may exhibit antiinflammatory effects in vivo, especially patients with bacterial infections including MAC diseases, through the modulation of M phi expression of some immunosuppressive cytokines.
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PMID:[Effects of secretory leukocyte protease inhibitor on the production of some cytokines and nitric oxide by murine peritoneal macrophages in response to lipopolysaccharide stimulation and M. avium complex infection]. 1048 11

Expression of secretory leukocyte protease inhibitor (SLPI) suppresses the ability of macrophages to respond to bacterial lipopolysaccharide (LPS). Here, addition of recombinant or native SLPI to the extracellular medium was non-suppressive, while transfection with a non-secretory form of SLPI was fully suppressive, an effect overcome by treatment with interferon-gamma. A portion of the SLPI produced by untransfected macrophages was localized in the cytosol. Thus, SLPI can act intracellularly to block macrophage activation by LPS.
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PMID:Suppression of macrophage responses to bacterial lipopolysaccharide by a non-secretory form of secretory leukocyte protease inhibitor. 1055 76


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