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)

In this report, we studied the effects of transforming growth factor (TGF)-beta 1 on lipopolysaccharide (LPS)-induced expression of endothelial cell (EC) adhesion molecules. Confluent human umbilical cord vein EC cultures were stimulated with Escherichia coli LPS and TGF-beta 1, alone or in combination for various times and evaluated for expression of ICAM-1, E-selectin, and VCAM-1 by immunofluorescence and radioimmunoassay. Effects of LPS and/or TGF-beta 1 on cell growth were also studied by 3H-thymidine incorporation. Both LPS and TGF-beta 1 alone stimulated EC expression of the adhesion molecules in a dose-dependent manner. The effects of TGF-beta 1 on LPS induction of the adhesion molecules varied with LPS concentration and treatment time, mode, and duration. Pretreatment with TGF-beta 1 for 24 h greatly augmented LPS induction of ICAM-1 and VCAM-1 expression, but decreased E-selectin expression. TGF-beta 1 also enhanced expression of the adhesion molecules in cells that were pretreated with 1 microgram/mL LPS for 60 min. Concomitant treatment with TGF-beta 1/LPS resulted in significant increases in ICAM-1 but decreases in VCAM-1 expression. TGF-beta 1 effects on LPS induction of the adhesion molecules were more prominent at lower LPS levels (.001, .01 microgram/mL). Both LPS and TGF-beta 1 suppressed thymidine incorporation in a dose-related pattern. These data suggest that TGF-beta 1 has additive and antagonistic effects on LPS induction of the adhesion molecules and that the cell responsiveness to the stimuli in the expression is related to growth condition of the cells. In conclusion, our findings suggest that TGF-beta 1 exhibits pro-inflammatory and anti-inflammatory activities in human endothelial cells and may play an important role in regulating leukocyte adherence and extravasation under LPS-induced inflammatory conditions.
 ...
PMID:Differential effects of transforming growth factor-beta 1 on lipopolysaccharide induction of endothelial adhesion molecules. 885 46

Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-beta and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-beta and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-beta and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-beta and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-beta and fibronectin than those from control subjects. The spontaneous release of TGF-beta is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-beta release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-beta in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma.
 ...
PMID:Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar macrophages in airway diseases. 887 Jul 8

Retinal inflammatory diseases in man are associated with an upregulation in the expression of intercellular adhesion molecule-1 (ICAM-1) in cells within the retina and with an increase in soluble ICAM-1 within the vitreous. These studies suggest that this protein may contribute to immunopathological processes within the eye. The effects of inflammatory mediators on the regulation of the expression and secretion of ICAM-1 by human retinal pigment epithelial cell cultures (HRPE) were investigated in order to identify the possible source of soluble ICAM-1 and the conditions which enhance its production. Immunofluorescence studies on TNF-alpha and/or IFN-gamma treated HRPE cells demonstrated cellular expression of ICAM-1 which was predominantly localized to intercellular junctions. Moreover, treatment of HRPE for 24 h with tumour necrosis factor alpha (TNF-alpha) (10 ng/ml), interferon gamma (IFN-gamma) (500 u/ml), interleukin 1 alpha (IL-1 alpha) (10 ng/ml) and IL-1 beta (10 ng/ml) results in the secretion of ICAM-1, ranging from 9 to 13 ng per 10(6) cells. IFN-gamma acts synergistically with (TNF-alpha) and IL-1 in the secretion of ICAM-1 by HRPE. Only 1.75 ng of soluble ICAM-1 was detected in untreated HRPE cells. In contrast, lipopolysaccharide (LPS), IL-6, IFN-alpha or TGF-beta did not exhibit any influence on ICAM-1 secretion by these cells. Northern blot analysis reveals an increased expression of ICAM-1 mRNA in HRPE stimulated with IFN-gamma, TNF-alpha or IL-1 for 24 h. In untreated cells, ICAM-1 mRNA is not detectable. There is a progressive increase in ICAM-1 mRNA levels in cytokine-treated HRPE, that reaches steady state by 12 h. Furthermore, a close correlation is noted between ICAM-1 mRNA levels and the secretion of ICAM-1 protein, suggesting regulation at the level of gene transcription. ICAM-1 secretion by RPE might actively participate in the immune reactions in the retina, by recruiting and activating lymphocytes, and contribute to the immunopathological processes in inflammatory diseases.
 ...
PMID:Inflammatory cytokines induce intercellular adhesion molecule-1 (ICAM-1) mRNA synthesis and protein secretion by human retinal pigment epithelial cell cultures. 889 37

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine that promotes IgA/IgG2b switching and secretion. Here, we show a differential effect of TGF-beta 1 on Ig production by lipopolysaccharide-stimulated spleen and lymph node (LN) B cells. Exogenous TGF-beta 1 increased IgA production in B cell cultures and IgG2b production by spleen B cells. In contrast, IgG2b was suppressed by TGF-beta 1 in cultures of LN B cells, although endogenous TFG-beta was required for IgG2b production in LN B cell cultures. The suppressor properties of exogenous TGF-beta 1 (0.5 ng/ml) on IgG2b production by LN B cells were also seen when testing IgG1 or IgG2a induced by interleukin-4 or interferon-gama, respectively. These differences between B cells from each lymphoid tissue appeared to be related to a different TGF-beta antiproliferative effect, since proliferation of LN B cells was extremely sensitive to TFG-beta 1 and IgG2b production was more sensitive than IgA to the TFG-beta-mediated suppression. However, by counteracting the antiproliferative effect of TGF-beta 1 with a CD40 agonistic mAb (IC10), the IgG2b response by LN B cells was still lacking. IC10 was nevertheless inhibitory for IgG2b production in most cases, while increasing secretion of IgA in the very same cultures. Taken together, the results suggest that functional differences between spleen and LN B cells do exit, at least with regard to the immunomodulating properties of TGF-beta on both proliferation and Ig production. Moreover, functional differences exist between cells committed for IgA and IgG2b regarding their sensitivity to the antiproliferative activity of TGF-beta 1 and the effect of CD40-derived signals on Ig secretion.
 ...
PMID:Differential effects of transforming growth factor-beta 1 on IgA vs. IgG2b production by lipopolysaccharide-stimulated lymph node B cells: a comparative study with spleen B cells. 889 46

Osteolysis has become a major cause of aseptic loosening in total joint arthroplasty (TJA). Titanium, cobalt and chromium are commonly used in orthopaedic implants (e.g. joint prostheses). The release of bone-associated cytokines has been associated with the development of osteolysis in patients with prostheses. We evaluated the effects of these metals on the release of bone-associated cytokines (IL-1 beta, IL-6, TNF-alpha and TGF-beta 1) by human blood monocytes/macrophages and monocyte-like U937 cells upon lipopolysaccharide (LPS) stimulation, the cell proliferation, and their cytotoxic effects on these cells in vitro. We found that the release of IL-1 beta was enhanced by titanium, chromium and cobalt, the release of TNF-alpha was enhanced by titanium and chromium, and the release of IL-6 was enhanced by titanium. All three metal ions inhibited the release of TGF-beta 1. We also found that titanium and chromium, but not cobalt, enhanced blood monocyte/macrophage proliferation in response to LPS while only titanium enhanced U937 cell proliferation in response to LPS. The metals in concentrations ranging from 0.01 to 100 ngml-1 did not stimulate the cells to secrete detectable cytokines in the absence of LPS. Furthermore, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to the metals did not alter cytokine release when the metals were removed from the media prior to the addition of LPS. Similarly, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to LPS did not alter cytokine release when LPS was removed from the media prior to the addition of the metals. The metals did not reduce cell viability and induce cell injury after 72h incubation with the cells. The data suggest that the three metals at clinically relevant concentrations modulated cytokine expression, whereas they did not induce any cytotoxic effects. A metal-induced enhancement of bone-resorbing cytokine release with a concomitant inhibition of bone-forming cytokine release may be an important factor in the development of osteolysis, which can severely compromise the outcome of TJA.
 ...
PMID:Titanium, chromium and cobalt ions modulate the release of bone-associated cytokines by human monocytes/macrophages in vitro. 896 17

Quiescent and non-quiescent human gingival fibroblasts (HGF) were incubated for 24 hours with Actinobacillus actinomycetemcomitans lipopolysaccharide (LPS) and/or growth factors (interleukin-1 beta [IL-1 beta], insulin, epidermal growth factor [EGF], platelet-derived growth factor [PDGF], fibroblast growth factor [FGF], and transforming growth factor-beta [TGF-beta]) to examine the ability of LPS to modify HGF proliferation in response to these autocrine and paracrine growth factors. A. actinomycetemcomitans LPS at high concentrations (> or = 9 micrograms/well) generally resulted in a reduction in DNA synthesis in quiescent and non-quiescent fibroblasts; however, LPS at low concentrations (< 9 micrograms/well) showed a minimal enhancement of DNA synthesis (40 to 60%) in quiescent and non-quiescent cells. HGF co-incubated with mitogenic agents and LPS (9 micrograms/well) exhibited suppression of growth factor-induced 3H-Tdr uptake compared to growth factor-stimulated controls. In contrast, 3H-Tdr uptake was slightly elevated with addition of LPS at low concentrations (0.09 microgram/well). These trends were seen with all growth factors tested. Non-quiescent cells, in general, were more responsive to the growth factors and LPS/growth factor combinations when compared to the quiescent HGF. HGF were further tested for the ability of LPS to alter growth factor responsiveness by pretreating the cells with LPS prior to incubation of the growth factor, as well as, subsequent addition of LPS to growth factor-pretreated cells. Similar patterns were observed as above, except IL-1 beta-pretreated quiescent and non-quiescent HGF followed by LPS addition demonstrated a marked elevation in proliferation when compared to IL-1 beta stimulated controls. These findings suggest that LPS may potentially modulate the proliferative rate of connective tissue undergoing inflammatory or growth factor-induced reparative processes in periodontal lesions.
 ...
PMID:The effect of lipopolysaccharide on growth factor-induced mitogenesis in human gingival fibroblasts. 899 73

Interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) exert protective effects during experimental endotoxemia through upregulation of cellular immunity and phagocytic functions. They are part of a positive regulatory feedback loop that enhances the production of the other. Because critically ill patients show a marked suppression of T-cell and macrophage functions with a high susceptibility to infection, potential defects in the immunity/inflammation upregulating IL-12 IFN-gamma pathway were studied. As an ex vivo model of endotoxemia, lipopolysaccharide (LPS) stimulated whole blood from 25 critically ill patients and 12 healthy individuals was incubated with either recombinant human (rh) IL-12 or rhIFN-gamma, respectively. IFN-gamma dose-dependently (P < .05) increased the release of IL-12 p40 and p70 into LPS-stimulated whole blood from healthy humans without effect in whole blood from critically ill patients. RhIL-12 p70 enhanced (P < .05) the secretion of IFN-gamma in controls, while it was ineffective in LPS-stimulated whole blood from critically ill patients. The observed inhibition of the IL-12 IFN-gamma pathway is not specific to LPS, since Staphylococcus aureus Cowan strain I (SAC)-stimulated whole blood from critically ill patients showed similar suppression. The secretion of IL-12 and IFN-gamma was less reduced in critically ill patients when using isolated cultures of adherent cells or lymphocytes. Although preculture of whole blood from healthy humans with IL-10, but not with IL-4, mimicked suppression of the IL-12 IFN-gamma pathway similar to that observed during critical illness, the release of antiinflammatory reacting cytokines (IL-4, IL-10, transforming growth factor [TGF]-beta 1) was decreased into LPS-stimulated whole blood from critically ill patients. These results indicate at least two mechanisms responsible for dramatic disturbances of the IL-12 IFN-gamma pathway during critical illness: (1) deactivation of IL-12 and IFN-gamma producing leukocytes in vivo early after the primary insult, and (2) presence of serum suppressive factors different from IL-4, IL-10, or TGF-beta 1. Because IL-12 and IFN-gamma upregulate essential immune functions, the marked inhibition of IL-12 and IFN-gamma release may be pivotal for high susceptibility of critically ill patients to infection.
 ...
PMID:Inhibition of the defense system stimulating interleukin-12 interferon-gamma pathway during critical Illness. 905 43

The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor beta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-beta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 +/- 1 y (mean +/- SD), with a body mass index (BMI; in kg/m2) of 17.2 +/- 0.5 and various noncancer disorders, and 22 healthy matched control subjects aged 72 +/- 1 y, with a BMI of 25.4 +/- 0.7 (significantly different from patients, P < 0.001), were included. Fifteen patients and their corresponding control subjects were reexamined 3 mo later. Isolated monocytes were stimulated with lipopolysaccharide (LPS) and concentrations of IL-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrations of IL-6, IL-1ra, IL-10, TGF-beta 1, and acute-phase reactants were analyzed. Serum concentrations of orosomucoid and IL-6 were higher in the malnourished subjects than in the control subjects (1.14 +/- 0.1 compared with 0.8 +/- 0.3 g/L, P < 0.001; and 5 ng/L compared with undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1 beta (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was found in monocytes from patients with PEM relative to the control subjects when monocytes were stimulated with 0.1 microgram LPS/L. Monocyte TNF generation and serum concentrations of IL-10, IL-1ra, and TGF-beta 1 did not differ. Similar results were obtained at follow-up. IL-1ra was negatively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cytokines such as IL-6 and IL-1 beta in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.
 ...
PMID:Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease. 906 43

Isotype switching is presaged by the transcriptional activation of the heavy chain class gene (CH) to which recombination will occur. As a result, mRNA or germline transcripts from the unrearranged gene accumulate in the cytoplasm. Previous studies demonstrated that transforming growth factor (TGF)-beta stimulated isotype switching to IgA in cultures of lipopolysaccharide (LPS)-stimulated murine B cells and increased the stability of C alpha mRNAs. The present study demonstrates that LPS-stimulated B cells express a 45 kDa protein, I alpha BP, that specifically binds to germline alpha transcripts. Following addition of TGF-beta, the binding activity of this protein is significantly reduced. The identification of a cytokine regulable RNA-binding protein that interacts with germline transcripts supports the idea that these transcripts are involved in recombination and raises the possibility that RNA-protein interactions play a role in regulating isotype switching.
 ...
PMID:A transforming growth factor-beta regulable RNA-binding protein interacts specifically with germline Ig alpha transcripts. 908 81

Nitric oxide (NO) and ornithine, products of NO synthase or arginase, respectively, have opposing biological activities. The effect of mediators of leukocyte activation and inhibition on arginine metabolism of resident mouse peritoneal exudate cells (MPEC) was determined. Factors that increased basal NO synthase activity, interferon (IFN)-gamma and lipopolysaccharide (LPS), decreased arginase activity in intact cells. Transforming growth factor (TGF)-beta1 decreased IFN-gamma-stimulated NO synthase activity and produced a reciprocal increase in urea and ornithine release. TGF-beta1 had no effect on the activity of these enzymes in LPS-stimulated MPEC. Corticosterone (Cort, 100 ng/ml) decreased the basal activity of both enzymes. However, Cort inhibited NO synthase activity and increased ornithine release in MPEC exposed to IFN-gamma or LPS. The difference between arginase activity in intact cells vs. that of cell lysates suggested intracellular inhibition of arginase activity. Products of NO synthase, NO and citrulline, were shown to inhibit MPEC arginase activity under maximal assay conditions. Intracellular pH was not altered by exposure of MPEC to LPS, IFN-gamma, TGF-beta, and Cort. This reciprocal change in arginine metabolism is proposed to be an important component of wound healing. Expression of NO synthase creates a cytotoxic environment that may be important to the early phase of wound healing. As wound healing progresses, increased arginase activity produces an environment favorable for fibroblast replication and collagen production.
 ...
PMID:Differential regulation of macrophage arginine metabolism: a proposed role in wound healing. 912 21


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