UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that primary human bronchial epithelial cells (HBECs) cultured on types I + III collagen were able to differentially regulate the production of major constitutive 92-kD gelatinase, minor 72-kD gelatinase, and their tissue-specific inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) in response to lipopolysaccharide (LPS) or proinflammatory cytokines, suggesting that HBECs may be involved in vivo in the active remodeling of the underlying extracellular matrix (ECM). In this study, we examined the possible effects of specific type IV collagen as compared with types I + III collagen on HBEC behavior and function. We investigated 92-kD gelatinase and TIMP-1 expression with zymography and reverse zymography, respectively, at the protein level, and with quantitative reverse transcription-polymerase chain reaction (RT-PCR) at the mRNA level. Results showed similar morphologic features and identical proliferation rates of HBECs in response to the two matrix substrates. Nevertheless, differences at the protein and mRNA levels between HBEC cultures on type IV collagen and on types I + III collagen included: (1) a lower basal level of 92-kD gelatinase production; (2) less upregulation of 92-kD gelatinase in response to LPS endotoxin or to the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha); and (3) loss of activation of the proforms of the 92-kD and 72-kD gelatinases. These findings, together with the maintenance of TIMP-1 expression, strongly suggest that type IV collagen used as a matrix substratum is associated with a homeostatic HBEC phenotype, and limits the ability of HBECs to degrade the matrix. In contrast, types I + III collagen may be associated with a matrix resorption phenotype corresponding to active matrix remodeling and repair. Thus, the ECM underlying HBECs may modulate matrix remodeling by HBECs, particularly in response to inflammatory processes during acute lung injury.
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PMID:Cell-matrix interactions modulate 92-kD gelatinase expression by human bronchial epithelial cells. 961 86

Type IX collagen (CIX), a cartilage-specific glycoprotein, constitutes < or = 10% of cartilage collagen. To ascertain whether CIX can induce arthritis as shown for type II and XI collagen (CII and CXI), outbred rats were sensitized with bovine, chick and human CIX; inbred rats, mice, and guinea pigs were sensitized with bovine CIX. Mice and guinea pigs proved resistant to arthritis, as did rats sensitized with CIX/Freund's incomplete adjuvant (FIA). Arthritis was seen in rats when 100 microg of Mycobacterium tuberculosis (Mtb) were added to FIA, but seldom with smaller doses of Mtb, suggesting the arthritis was adjuvant-induced. High levels of antibodies to rat CIX, containing complement-fixing subclasses, were detected in rat sera in addition to DTH and lymphocyte proliferation responses to rat CIX. Given the potential for CIX-induced disease, CIX-sensitized rats were injected intraperitoneally with lipopolysaccharide (LPS) to stimulate proinflammatory cytokine release, and intra-articularly with rat CIX to stimulate arthritis. LPS stimulation was ineffective; however, intra-articularly injected CIX produced transient synovitis. When rats with stable adjuvant arthritis were sensitized with CIX/FIA, significant increases in paw volume were measured compared with controls given CI/FIA. Immunohistochemical studies of actively and passively sensitized rats revealed deposits of CIX antibody, but not C3, at the joint margins where proteoglycan staining was weak. Together, these findings suggest that autoimmunity to CIX, in contrast to CII and CXI, is not directly pathogenic but may contribute to joint injury provided arthritis is initiated by an independent disease process.
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PMID:Immunity to type IX collagen in rodents: a study of type IX collagen for autoimmune and arthritogenic activities. 964 4

Dendritic cells (DC) are potent antigen presenting cells, which are responsible for the initiation of naive T and T-dependent immune responses. The present studies were based upon recent reports that commercial collagen I preparations induce the maturation of human DC in vitro. We show that human blood monocyte-derived (GM-CSF and IL-4 cultured) DC pulsed on collagen I-coated plates undergo a dose-dependent increase in stimulatory capacity in oxidative mitogenesis assays. This is accompanied by the upregulation of costimulatory molecules (CD40, CD80, CD86), CD25, ICAM-1 and the DC-specific marker CD83. The maturation effect is more potent than TNF-alpha, which is a known mediator of DC function. However, bacterial lipopolysaccharide (LPS), a powerful inducer of DC maturation, was found to be present at very high levels in one commercial collagen solution that was tested. The effect of LPS upon DC maturation was similar to culture with collagen. Furthermore, a different collagen I preparation with low levels of LPS contamination was less effective at inducing DC maturation, while spiking the collagen solution with LPS prior to plastic coating equalised these effects. Finally, human monocyte-derived DC were found not to express typical collagen receptors VLA-1, 2 and 3. We therefore propose that LPS contamination may at least partially explain reported collagen I induced DC maturation.
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PMID:Bacterial lipopolysaccharide contamination of commercial collagen preparations may mediate dendritic cell maturation in culture. 969 67

In this study, Escherichia coli lipopolysaccharide (LPS) dose-dependently (100-300 microg/ml) and time-dependently (10-60 min) inhibited platelet aggregation in human platelets stimulated by agonists. LPS also dose-dependently inhibited the phosphoinositide breakdown and the intracellular Ca+2 mobilization in human platelets stimulated by collagen. LPS (300 microg/ml) also significantly inhibited the thromboxane A2 formation stimulated by collagen in human platelets. Moreover, LPS (100-300 microg/ml) dose-dependently decreased the fluorescence of platelet membranes tagged with diphenylhexatrience. In addition, LPS (200 and 300 microg/ml) significantly increased the formation of cyclic GMP but not cyclic AMP in platelets. LPS (200 microg/ml) also significantly increased the production of nitrate within a 30 min incubation period. Rapid phosphorylation of a platelet protein of Mr 47,000, a marker of protein kinase C activation, was triggered by phorbol-12-13-dibutyrate (PDBu, 50 nM). This phosphorylation was markedly inhibited by LPS (200 microg/ml) within a 30 min incubation period. These results indicate that the antiplatelet activity of LPS may be involved in two important pathways. (1) LPS may induce conformational changes in the platelet membrane, leading to change in the activity of phospholipase C. (2) LPS also activated the formation of nitric oxide (NO)/cyclic GMP in human platelets, resulting in inhibition of platelet aggregation. Therefore, LPS-mediated alteration of platelet function may contribute to bleeding diathesis in septicaemic and endotoxaemic patients.
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PMID:Mechanisms involved in the antiplatelet activity of Escherichia coli lipopolysaccharide in human platelets. 979 85

An in vitro model consisting of endothelium grown on collagen was used to investigate how mononuclear phagocytes traverse endothelium in the basal-to-apical direction (reverse transmigration), a process that mimics their migration across vascular and/or lymphatic endothelium during atherosclerosis and resolution of inflammation, respectively. Monoclonal antibody (MoAb) VIC7 against tissue factor (TF) inhibited reverse transmigration by 77%. Recombinant tissue factor fragments containing at least six amino acids C-terminal to residue 202 also strongly inhibited reverse transmigration. TF was absent on resting monocytes but was induced on these cells after initial apical-to-basal transendothelial migration. Two additional observations suggest that TF is involved in adhesion between mononuclear phagocytes and endothelium: (1) when monocytes were incubated with lipopolysaccharide (LPS) to stimulate expression of TF before they were added to endothelium, VIC7 or soluble TF modestly inhibited their adhesion to the apical endothelial surface, each by about 35%; and (2) endothelial cells specifically bound to surfaces coated with TF fragments containing amino acids 202-219. This binding was blocked by anti-TF MoAb, suggesting that endothelial cells bear a receptor for TF. These data suggest that mononuclear phagocytes use TF, perhaps as an adhesive protein, to exit sites of inflammation.
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PMID:Role of tissue factor in adhesion of mononuclear phagocytes to and trafficking through endothelium in vitro. 983 21

Am-80 is a newly snythesized retinoid with the structure of one aromatic amide among retinobenzoic acids. It exhibits specific biological activities of retinoic acid such as the activation of cellular differentiation and proliferation. We investigated the effect of Am-80 on collagen-induced arthritis (CIA) in mice and the immunopharmacological action on the production of several cytokines in the in vitro and in vivo models. Am-80, at doses of 0.3, 1 and 3 mg/kg, significantly inhibited the severity and development of the arthritis index, progression of foot pad swelling, bone damage and histopathological alterations. Am-80 also inhibited the production of anti-type II collagen (CII) IgG antibody, but did not affect the delayed-type hypersensitivity (DTH) response in arthritic mice. To determine the inhibitory mechanism of Am-80, we studied the effect of Am-80 on the production of cytokines. Am-80 did not affect the production of IFN-gamma by Th1 cells (1E10.H2 cells) and IL-4 by Th2 cells (D10.G4.1 cells), respectively. Am-80 selectively inhibited bacterial lipopolysaccharide (LPS)-induced IL-6, but not TNF-alpha and IL-1beta, production in mice. Moreover Am-80 inhibited IL-1beta induced IL-6 production and IL-6 mRNA expression in human osteoblast-like cells (MG-63). The inhibition of IL-6 production by Am-80 was due to downregulation of the pretranscription or the transcription of IL-6 in MG 63 cells. These findings suggest that the inhibitory effect of Am-80 on CIA is partially by modulating the production of the proinflammatory cytokine, IL-6.
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PMID:Effect of Am-80, a synthetic derivative of retinoid, on experimental arthritis in mice. 987 34

Fibroblasts are important effector cells having a potential role in augmenting the inflammatory responses in various diseases. In infantile diarrhea caused by enteropathogenic Escherichia coli (EPEC), the mechanism of inflammatory reactions at the mucosal site remains unknown. Although the potential involvement of fibroblasts in the pathogenesis of cryptococcus-induced diarrhea in pigs has been suggested, the precise role of lamina propria fibroblasts in the cellular pathogenesis of intestinal infection and inflammation caused by EPEC requires elucidation. Earlier we reported the lipopolysaccharide (LPS)-induced cell proliferation, and collagen synthesis and downregulation of nitric oxide in lamina propria fibroblasts. In this report, we present the profile of cytokines and adhesion molecules in the cultured and characterized human small intestinal lamina propria fibroblasts in relation to neutrophil migration and adhesion in response to lipopolysaccharide (LPS) extracted from EPEC 055:B5. Upon interaction with LPS (1-10 micrograms/ml), lamina propria fibroblasts produced a high level of proinflammatory mediators, interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and cell adhesion molecules (CAM) such as intercellular cell adhesion molecule (ICAM), A-CAM, N-CAM and vitronectin in a time-dependent manner. LPS induced cell-associated IL-1alpha and IL-1beta, and IL-6, IL-8 and TNF-alpha as soluble form in the supernatant. Apart from ICAM, vitronectin, A-CAM, and N-CAM proteins were strongly induced in lamina propria fibroblasts by LPS. Adhesion of PBMC to LPS-treated lamina propria fibroblasts was ICAM-dependent. LPS-induced ICAM expression in lamina propria fibroblasts was modulated by whole blood, PBMC and neutrophils. Conditioned medium of LPS-treated lamina propria fibroblasts remarkably enhanced the neutrophil migration. The migration of neutrophils was inhibited by anti-IL-8 antibody. Co-culture of fibroblasts with neutrophils using polycarbonate membrane filters exhibited time-dependent migration of neutrophils. These findings indicate that the coordinate production of proinflammatory cytokines and adhesion molecules in lamina propria fibroblasts which do not classically belong to the immune system can influence the local inflammatory reactions at the intestinal mucosal site during bacterial infections and can influence the immune cell population residing in the lamina propria.
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PMID:Interaction of lipopolysaccharide with human small intestinal lamina propria fibroblasts favors neutrophil migration and peripheral blood mononuclear cell adhesion by the production of proinflammatory mediators and adhesion molecules. 1003 24

Arginase, which catalyzes the conversion of arginine to urea and ornithine, and consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Arginine is also used for the synthesis of nitric oxide and creatine phosphate, while ornithine is used for the synthesis of polyamines and proline, and thus collagen. Arginase II mRNA and protein are abundant in the intestine (most abundant in the jejunum and less abundant in the ileum, duodenum, and colon) and kidney of the rat. In the kidney, the levels of arginase II mRNA do not change appreciably from 0 to 8 weeks of age. In contrast, arginase II mRNA and protein in the small intestine are not detectable at birth, appear at 3 weeks of age, the weaning period, and their levels increase up to 8 weeks. On the other hand, mRNAs for ornithine aminotransferase (OAT), ornithine decarboxylase, and ornithine carbamoyltransferase (OCT) are present at birth and their levels do not change much during development. Arginase II is elevated in response to a combination of bacterial lipopolysaccharide, dibutyryl cAMP, and dexamethasone in the kidney, but is not affected by these treatments in the small intestine. Immunohistochemical analysis of arginase II, OAT, and OCT in the jejunum revealed their co-localization in absorptive epithelial cells. These results show that the arginase II gene is regulated differentially in the small intestine and kidney, and suggest different roles of the enzyme in these two tissues. The co-localization of arginase II and the three ornithine-utilizing enzymes in the small intestine suggests that the enzyme is involved in the synthesis of proline, polyamines, and/or citrulline in this tissue.
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PMID:Expression of arginase II and related enzymes in the rat small intestine and kidney. 1005 48

Transforming growth factor-beta1 (TGF-beta1) is a powerful stimulus for collagen formation in vitro. To determine the in vivo effects of TGF-beta1 on liver fibrogenesis, we generated transgenic mice overexpressing a fusion gene [C-reactive protein (CRP)/TGF-beta1] consisting of the cDNA coding for an activated form of TGF-beta1 under the control of the regulatory elements of the inducible human CRP gene promoter. Two transgenic lines were generated with liver-specific overexpression of mature TGF-beta1. After induction of the acute phase response (15 h) with lipopolysaccharide (100 microgram ip), plasma TGF-beta1 levels reached >600 ng/ml in transgenic animals, which is >100 times above normal plasma levels. Basal plasma levels of uninduced transgenic animals were about two to five times above normal. As a consequence of hepatic TGF-beta1 expression, we could demonstrate marked transient upregulation of procollagen I and procollagen III mRNA in the liver 15 h after the peak of TGF-beta1 expression. Liver histology after repeated induction of transgene expression showed an activation of hepatic stellate cells in both transgenic lines. The fibrotic process was characterized by perisinusoidal deposition of collagen in a linear pattern. This transgenic mouse model gives in vivo evidence for the important role of TGF-beta1 in stellate cell activation and liver fibrogenesis. Due to the ability to control the level of TGF-beta1 expression, this model allows the study of the regulation and kinetics of collagen synthesis and fibrolysis as well as the degree of reversibility of liver fibrosis. The CRP/TGF-beta1 transgenic mouse model may finally serve as a model for the testing of antifibrogenic agents.
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PMID:TGF-beta1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis. 1019 51

Endothelial cells express a variety of receptor systems involved in humoral defense, including receptors for the collagen-like and globular domains of the complement component C1q, designated cC1qR and gC1qR, respectively. In the present study a microvascular endothelial cell line was used to test the hypothesis that expression of these C1q-binding proteins may be affected by vascular inflammatory reactions. The results demonstrate that the expression of both cC1qR and gC1qR by bone marrow vascular endothelial cells is up-regulated by inflammatory mediators, interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide (Escherichia coli, 055:B5) in a dose- and time-dependent manner, as detected by enzyme-linked immunosorbent assay. cC1qR and gC1qR expression increased significantly (P < .05) within 4 to 7 hours and doubled after 22 hours of stimulation. 3H-thymidine incorporation studies and direct cell counts confirmed that increased C1qR expression was not due to increased cell proliferation. Northern blot analysis revealed that the up-regulation of cC1qR and gC1qR protein expression was preceded by increases in corresponding mRNA levels, suggesting increased gene transcription. Indeed C1qR mRNA up-regulation was prevented by actinomycin D, and C1qR protein synthesis was inhibited by cycloheximide. Bone marrow vascular endothelial cell exposure to C1q, however, did not alter cC1qR or gC1qR expression, but up-regulation of the leukocyte adhesion molecule ICAM-1 was noted in the presence of aggregated C1q. The up-regulation of C1qR by inflammatory mediators and the ability of C1q itself to increase ICAM-1 expression suggest a potential role for these binding sites in vascular inflammation and immune injury.
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PMID:Up-regulation of endothelial cell binding proteins/receptors for complement component C1q by inflammatory cytokines. 1036 Jun 24

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