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

Little is known on the forms of interleukin-1beta (IL-1beta) that are produced by microglial cells in the nervous system. Mixed glial cell cultures of rats produced IL-1beta in response to lipopolysaccharide (LPS). Using Western blot, pro-IL-1beta was found to be localized both intracellularly and in the supernatant, whereas mature IL-1beta was found only in the supernatant but in lower quantities than pro-IL-1beta. Immunocytochemistry confirmed that microglial cells are the exclusive source of IL-1beta. Blockade of the IL-1beta-converting enzyme (ICE) by Tyr-Val-Ala-Asp-aldehyde (YVAD-CHO) decreased the levels of mature IL-1beta but had no effect on pro-IL-1beta. Release of pro-IL-1beta was not associated with cell death nor with the extracellular release of ICE. Using gelatin zymography, glial cells were found to express constitutive matrix metalloproteinases (MMP) in the form of MMP-2. Exposure to LPS induced MMP-9 expression in a time-dependent manner similar to the pro-IL-1beta expression profile. MMP activation and inhibition experiments indicated a possible role of MMPs in the cleavage of pro-IL-1beta but not in the generation of mature IL-1beta. Microglial cells share with macrophages the ability to release large amounts of pro-IL-1beta of which the extracellular role remains to be determined.
 ...
PMID:Rat microglial cells secrete predominantly the precursor of interleukin-1beta in response to lipopolysaccharide. 1155 86

The pathogenesis of pseudomonal keratitis was investigated by focusing on induction and activation of matrix metalloproteinases (MMPs) by pseudomonal virulence factors and proinflammatory cytokines. Corneal lesions and MMP induction in vivo were evaluated in rabbit corneas infected with a clinical isolate of Pseudomonas aeruginosa. Effects of pseudomonal virulence factors [elastase, alkaline protease, exotoxin A and lipopolysaccharide (LPS)], tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta on MMP induction and activation were further examined in vitro in rabbit corneal fibroblasts (RCF) and human fibrosarcoma (HT1080) cells using reverse transcriptase-polymerase chain reaction (RT-PCR), zymography and immunoblotting. Corneal ulcers with typical ring abscesses were observed 12-24 h after infection, and MMPs, particularly MMP-9, were upregulated in infected corneas. Pseudomonal elastase caused the most extensive damage to both cell types. RCF treated with pseudomonal exoproteases or LPS expressed and secreted MMP-9. Exotoxin A had no effect on MMP expression. Both IL-1beta and TNF-alpha augmented MMP-9 expression in HT1080 cells. Pseudomonal elastase proteolytically activated MMP-2 and MMP-9 released from the cells. In conclusion, corneal destruction seen with P. aeruginosa infections may result from enhanced expression of MMPs by corneal stromal cells stimulated with pseudomonal exoproteases and proinflammatory cytokines and the proteolytic activation of MMPs by pseudomonal elastase.
 ...
PMID:Matrix metalloproteinases induction by pseudomonal virulence factors and inflammatory cytokines in vitro. 1174 75

We report the effects of mouldy hay/straw exposure, inhaled hay dust suspension (HDS) and inhaled lipopolysaccharide (LPS) on bronchoalveolar lavage fluid (BALF) gelatinolytic matrix metalloproteinase (MMP) levels and degree of activation in healthy (n = 6) and heaves- (previously termed chronic obstructive pulmonary disease) affected (n = 6 or 7) horses. Gelatinolytic MMPs in BALF were quantified by zymography, and gelatinases were shown by Western immunoblotting to be MMP-2 and MMP-9. Hay/straw and HDS challenges increased BALF total gelatinolytic activity only in heaves horses, with the majority of gelatinolytic activity comprising pro- and active MMP-9. The 5 h duration hay/straw challenge increased BALF gelatinolytic MMP activity in heaves horses at 5 and 24 h after the start of this challenge, with activity returning to baseline by Day 4. In contrast to hay/straw and HDS challenges, LPS inhalation increased BALF gelatinolytic MMP activity in both groups. For all challenges, absolute BALF neutrophil counts were highly significantly correlated (P<0.0001) with levels of proMMP-9 and active MMP-9, but not with levels of MMP-2 (P>0.05). As gelatinolytic MMPs are pro-inflammatory agents, they may contribute to lung dysfunction and tissue destruction in heaves horses exposed to airborne organic stable dusts.
 ...
PMID:Inhalation of organic dusts and lipopolysaccharide increases gelatinolytic matrix metalloproteinases (MMPs) in the lungs of heaves horses. 1190 57

Matrix metalloproteinases (MMPs) and transforming growth factor (TGF)-beta are involved in airway remodeling associated with the inflammatory process. In this study, we investigated the effect of RP 73-401 (piclamilast), a selective phosphodiesterase-4 inhibitor, on MMP-9 activity and TGF-beta production in two murine models of acute inflammation. In the first model, the lipopolysaccharide (LPS)-induced increase in neutrophils, MMP-9 activity, and tumor necrosis factor (TNF)-alpha and TGF-beta release in bronchoalveolar lavage (BAL) was significantly reduced by RP 73-401 pretreatment. In contrast, the BAL interleukin (IL)-10 level was decreased by LPS but restored by RP 73-401. IL-10 administration in LPS-exposed mice elicited a significant reduction in BAL neutrophilia, MMP-9 activity, and TNF-alpha release but not in TGF-beta production. In the second model, RP 73-401 inhibited BAL neutrophils but not MMP-9 activity and TGF-beta production that were induced by intranasal TNF-alpha. We demonstrated that RP 73-401 might modulate the expression of airway remodeling-associated mediators such as MMP-9 and TGF-beta and that this effect seemed to be at least partially mediated by the balance between TNF-alpha and IL-10.
 ...
PMID:The selective phosphodiesterase 4 inhibitor RP 73-401 reduced matrix metalloproteinase 9 activity and transforming growth factor-beta release during acute lung injury in mice: the role of the balance between Tumor necrosis factor-alpha and interleukin-10. 1190 82

Neuroinflammation induces a complex molecular cascade that leads to the proteolysis of cells. Matrix metalloproteinases (MMPs) attack all components of the extracellular matrix in a number of neuroinflammatory diseases and cause a delayed opening of the blood-brain barrier (BBB). Earlier, we showed that lipopolysaccharide (LPS) disrupted the BBB through the action of gelatinase B (MMP-9). In a study of cerebral ischemia, gelatinase A (MMP-2) was seen in astrocytic end-feet and stromelysin-1 (MMP-3) in microglia. Since other MMPs may be important in LPS-induced injury, we studied the gene transcription and cellular localization of several MMPs and an inflammatory mediator, tumor necrosis factor (TNF-alpha), using competitive polymerase chain reaction (PCR) and immunohistochemical methods. Significantly elevated levels of MMP-2 and -3 mRNA were observed in LPS-injected brains by 2 h after injection as compared to non-injected brain tissue (P<0.05). By 8 h post-LPS injection, gene expression of MMP-2 and -3 had declined in both saline- and LPS-injected tissue, while TNF-alpha mRNA levels rose significantly. Immunohistochemistry of control brains confirmed the earlier observation of MMP-2 immunoreactivity in processes abutting cerebral blood vessels, which increased after LPS injection. The expression of MMP-9 and MMP-3 was localized mainly to the cerebrovasculature in LPS-stimulated brain tissue, predominantly in the perivascular cells of the basal lamina near the site of injection. Both of these proteinases were present at the site of LPS injection at 8 h, but MMP-2 was absent. Our results show that MMP genes are up-regulated prior to the induction of cytokines such as TNF-alpha, and that MMP proteins are prominent around blood vessels in LPS-induced neuroinflammation.
 ...
PMID:Stromelysin-1 and gelatinase A are upregulated before TNF-alpha in LPS-stimulated neuroinflammation. 1192 34

Destruction of lung elastin is critical for development of emphysema associated with chronic obstructive pulmonary disease (COPD). Lung macrophages release elastolytic enzymes, including matrix metalloproteinase (MMP)-9, along with tissue inhibitors of MMP (TIMP). We examined the production and activity of macrophage-derived MMP-9 and TIMP-1 from alveolar macrophages (AM) from smokers with COPD, healthy smokers (HS), and nonsmokers (NS). AM were stimulated with either lipopolysaccharide (LPS), interleukin (IL)-1 beta, or cigarette smoke-conditioned culture medium (CSM). AM from patients with COPD released greater amounts of MMP-9 with greater enzymatic activity than HS and NS. In contrast, AM from NS released more TIMP-1 than cells from HS and subjects with COPD. LPS and IL-1 beta caused a dose-dependent increase in MMP-9 release and activity, together with increased levels of TIMP-1. Dexamethasone prevented the increase in MMP-9 release, and increased TIMP-1 release. CSM increased MMP-9 and TIMP-1 release from AM of all groups. Dexamethasone decreased CSM-stimulated MMP-9 release, but had no effect on MMP-9 activity This study suggests that macrophages might be important in the development of COPD because these cells exhibit increased levels of elastolytic activity.
 ...
PMID:Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. 1197 Sep 13

Protease-activated receptor-2 (PAR2) acts as a receptor for trypsin and trypsin-like enzymes. The role of this receptor in airway inflammation is uncertain. In this study we assessed the effect of activation of PAR2 following intranasal administration of the peptide activator of PAR2, SLIGRL, over 72 h in mice. The extent of immune cell infiltration into the airways and activities of matrix metalloprotease-2 (MMP-2) and MMP-9 were assessed in bronchoalveolar lavage (BAL) by differential cell counts and gelatin zymography, respectively. SLIGRL did not cause a change in the number or types of cells retrieved in BAL at any time point and did not alter the levels of MMP-2 and MMP-9 present in BAL. In contrast, similar intranasal administration of bacterial lipopolysaccharide (LPS) caused a large influx of neutrophilic polymorphonuclear leukocytes, which was associated with increased MMP-2 at 3 h only and MMP-9 activity from 3-72 h. Simultaneous administration of SLIGRL and LPS transiently potentiated increased MMP-9 activity at 3 h but markedly inhibited neutrophil influx and elevated MMP-2 activity at 3 h. These findings suggest that PAR2 agonists may be useful therapeutic molecules in pulmonary inflammatory diseases.
 ...
PMID:Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice. 1203 66

The objective of this study is to determine the biological effects of various antiadhesion agents on macrophages, which play an essential role in wound healing and adhesion. To determine these effects, RAW264.7 macrophages were activated with lipopolysaccharide in the presence of antiadhesion agents: oxidized regenerated cellulose (oxyC), sodium hyaluronate (HA), dexamethasone (Dex), or chondroitin sulfate (CS). The release of nitric oxide (NO), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), or matrix metalloproteinases (MMPs) from RAW264.7 was measured. We found that oxyC reduced the release of NO, IL-6, MMP-2, and MMP-9, whereas it enhanced the release of VEGF. HA reduced the release of MMP-2, whereas it enhanced the release of VEGF and NO. HA exhibited no significant effect on the release of IL-6 or MMP-9. Dex reduced the release of NO, VEGF, IL-6, MMP-2, and MMP-9. CS reduced the release of VEGF, IL-6, and MMP-2, although it had no significant effect on the release of NO and MMP-9. Antiadhesion agents, which have been clinically used as physical barriers, modulated the functions of macrophages.
 ...
PMID:The biological effects of antiadhesion agents on activated RAW264.7 macrophages. 1211 53

Glucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Cartilage discs (3.5 mm) were biopsied and cultured. Explants were incubated with lipopolysaccharide (LPS) in the presence of varying concentrations of GLN, CS, or both. Control treatments included explants with no LPS and LPS without GLN or CS. Media were analysed for nitric oxide (NO), prostaglandin E2 (PGE2) and keratan sulphate. Cartilage was extracted for analysis of metalloproteinases (MMP). Four experiments were conducted. In all experiments, GLN at concentrations as low as 1 mg/ml decreased NO production relative to LPS stimulated cartilage without GLN over the 4 day period. In general, CS at either 0.25 or 0.5 mg/ml did not inhibit NO production. The addition of CS to GLN containing media did not further inhibit NO production. GLN at concentrations as low as 0.5 mg/ml decreased PGE2 production, whereas CS did not effect on PGE2. The combination of GLN/CS decreased MMP-9 gelatinolytic activity but had no effect on MMP-2 activity. The combination in 2 experiments tended to decrease MMP-13 protein concentrations and decreased keratan sulphate levels in media. Overall, the combination of GLN (1 mg/ml) and CS (0.25 mg/ml) inhibited the synthesis of several mediators of cartilage degradation. These results further support the effort to understand the role of GLN and CS in preserving articular cartilage in athletic horses.
 ...
PMID:Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate. 1240 91

Prevotella intermedia, a Gram-negative obligate anaerobic black-pigmented oral bacterium, belongs to a small group of microorganisms that is closely associated with the initiation of periodontal diseases. Lipopolysaccharide (LPS), an outer membrane component, is one of the main virulence factors of this bacterium. The aim of this study was to examine the effects of Prev. intermedia lipopolysaccharide, extracted by the hot-phenol-water method, on differentiation (alkaline phosphatase activity) and mineralisation (calcium incorporation) of fetal mouse calvarial cells in vitro and to determine the release of the important osteolytic factors nitric oxide, interleukin-6 (IL-6) and matrix metalloproteinases by these cells after treatment with different concentrations of Prev. intermedia lipopolysaccharide (0.2-25 microg/ml). By gelatin zymography, we also characterized the matrix metalloproteinases released by these osteoblasts. Treatment with Prev. intermedia lipopolysaccharide dose-dependently inhibited bone formation by reducing alkaline phosphatase activity and calcium incorporation and induced the release of nitric oxide, IL-6 and the latent proforms of MMP-2 and MMP-9 by fetal mouse osteoblasts in organoid culture. These results indicate that the lipopolysaccharide from Prev. intermedia not only participates in periodontal tissue destruction and alveolar bone resorption, but also inhibits bone formation.
 ...
PMID:Effects of lipopolysaccharide extracted from Prevotella intermedia on bone formation and on the release of osteolytic mediators by fetal mouse osteoblasts in vitro. 1245 May 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>