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)

The in vitro formation of fibrin microclots in blood from patients with psoriasis was studied before, during and after treatment. When a bacterial lipopolysaccharide was added to the blood, the microclot test was positive in 0% of controls, in 17% of the patients with untreated slight psoriasis and in 100% of those with severe psoriasis. A positive test without added lipopolysaccharide indicates the presence of circulating endotoxins. It was negative in all patients with slight psoriasis but positive in 75% of those with a severe form. During treatment the microclots decreased concurrently with clinical improvement in 79% of the patients. After treatment, eleven patients still had a positive test and nine of these patients showed a relapse within 1-2 months. Warfarin treatment rapidly inhibited microclot formation but this had little or no effect on the psoriatic lesions. High doses of potent corticosteroids under occlusion inhibited microclot formation for some hours. It seems likely that there may be a release of endotoxins in severe psoriasis which is decreased during successful treatment.
Br J Dermatol 1983 Jan
PMID:The influence of treatment on fibrin microclot generation in psoriasis. 682 42

Chemokinesis and chemotaxis of neutrophil leucocytes were studied by migration under agarose in 35 patients with psoriasis and compared with 35 healthy controls. Eschericheae coli filtrate and lipopolysaccharide were used as chemo-attractants. Of these patients, 14 were tested before and after photochemotherapy. The chemotactic capacities of psoriatic serum before and after PUVA therapy were also investigated. The increase in the chemotactic activity of psoriatic polymorphonuclear leucocytes (PMNs) was not significant and remained unchanged after PUVA therapy. The activated psoriatic serum showed a slight increase in chemotactic activity when compared with normal activated serum. These results do not support an intrinsic abnormality of psoriatic PMNs, and their migration into psoriatic lesions could be chiefly due to the presence of chemotactic factors in involved epidermis.
Arch Dermatol Res 1983
PMID:Neutrophil chemotaxis in psoriasis before and after PUVA therapy. 684 41

E-selectin is an inducible endothelial cell adhesion protein that is a critical element in the binding of leukocytes to activated endothelial cells. It is induced by a variety of pro-inflammatory soluble substances including interleukin-1 (IL-1), tumor necrosis factor (TNF), or bacterial lipopolysaccharide (LPS). In vitro studies of a large vessel endothelial cells demonstrate that stimulation with TNF or IL-1 leads to a rapid, but transient, induction of E-selectin expression that disappears within 24 hours. However, in vivo studies have shown that microvascular endothelial cells persistently express E-selectin in chronic inflammatory states, particularly in the skin where it serves as a homing receptor for memory T cells. Stimulation of dermal-derived microvascular endothelial cells (HDMECs) with single doses of IL-1 alpha, TNF alpha, or LPS resulted in transient but slightly more persistent expression of E-selectin than seen after stimulation of large vessel derived umbilical vein endothelial cells (HUVECs). However, stimulation of either HDMECs or HUVECs with repetitive doses of IL-1 alpha, TNF alpha, or LPS in the presence of human serum or plasma resulted in persistent E-selectin expression in vitro. The persistent E-selectin cell surface expression was associated with persistent E-selectin mRNA expression and correlated with E-selectin-mediated HL-60 binding to endothelial cell monolayers. The effect of human plasma or serum was dose dependent, and fractionation of human plasma by gel filtration demonstrated that the E-selectin persistence activity resolved into high and low molecular peaks. These data demonstrate that human endothelial cells are capable of persistent E-selectin expression in vitro and that factors in human serum or plasma are critical in preventing cytokine refractoriness and loss of E-selectin expression. This study provides a basis to resolve the apparent discrepancies between previous in vivo and in vitro dynamics of E-selectin expression.
J Invest Dermatol 1994 Apr
PMID:A factor in human plasma permits persistent expression of E-selectin by human endothelial cells. 751 14

In many inflammatory dermatoses leukocyte function-associated antigen-1/intercellular adhesion molecule-1 mediated T-cell/keratinocyte adhesion is considered to play an important role. Pentoxifylline (PTX), a methylxanthine derivative widely used for the symptomatic treatment of various vascular disorders, was recently found to have anti-inflammatory effects. PTX can suppress tumor necrosis factor-alpha production and function, and inhibits leukocyte-endothelial cell adherence. The aim of the present study was to investigate whether PTX also interferes with T-cell/keratinocyte binding. Peripheral blood T cells were activated with phorbol myristate acetate and co-incubated with interferon-gamma- or tumor necrosis factor-alpha-stimulated keratinocytes (SVK 14 cells) in the presence or absence of PTX. Using an enzyme-linked immuno cell adhesion assay PTX was found to inhibit T-cell/keratinocyte adhesion in a dose-dependent manner. A similar inhibition was found when PTX was replaced by isobutylmethylxanthine, another methylxanthine derivative, or by a combination of two cyclic adenosine monophosphate analogues. No major effect on T-cell/keratinocyte adherence was observed when PTX was present during the pre-incubation of keratinocyte monolayers with tumor necrosis factor-alpha or interferon-gamma prior to the adhesion assay. In keratinocyte monolayers the interferon-gamma or tumor necrosis factor-alpha induced intercellular adhesion molecule-1 expression could not be inhibited by PTX. However, when PTX was added to short-term organ cultures of normal human skin biopsies, the lipopolysaccharide- and tumor necrosis factor-alpha-induced keratinocyte intercellular adhesion molecule-1 expression was blocked completely. The interferon-gamma-induced ICAM-1 expression was not blocked by PTX. The results presented herein suggest that impaired T-cell/keratinocyte binding may be one of the mechanisms by which PTX exerts a beneficial effect in certain inflammatory dermatoses.
J Invest Dermatol 1995 Jun
PMID:Pentoxifylline inhibits T-cell adherence to keratinocytes. 753 68

It has been suggested that in atopic eczema (AE) a reduced lymphocyte response to T-cell mitogens in vitro is secondary to altered production of cytokines or inflammatory mediators. We investigated, in parallel, the mitogen-induced T-cell proliferation, monocyte interleukin-1 beta (IL-1 beta) production, and prostaglandin E2 (PGE2) production of monocytes and of peripheral blood mononuclear cells (PBMC) in AE patients and non-atopic controls. After stimulation with concanavalin A (Con A) PBMC of AE patients showed a significantly reduced proliferative response compared with the controls. The monocyte production of IL-1 beta after stimulation with lipopolysaccharide (LPS) was significantly decreased in AE. No differences between AE patients and controls were observed with regard to the PGE2 production of PBMC after stimulation with Con A or the monocyte release of PGE2 after LPS stimulation. Because IL-1 plays a central role in the activation of T-cell proliferation, the decreased monocyte IL-1 beta production may provide a plausible explanation for the reduced mitogen response of T cells in AE.
Br J Dermatol 1995 Mar
PMID:Decreased monocyte interleukin-1 beta production in atopic eczema. 771 54

The regulatory effect of endogenously synthesized eicosanoid metabolites on the expression of tissue inhibitor of metalloproteinases (TIMP), interstitial collagenase, and 92-kDa gelatinase by human macrophages was examined. TIMP and metalloproteinase production were stimulated with three agonists that produce distinct patterns of eicosanoid synthesis: lipopolysaccharide (10 micrograms/ml), denatured collagen (10 micrograms/ml), or zymosan (1 mg/ml). Indomethacin (3 micrograms/ml) or MK886 (3 microM), a specific inhibitor of 5-lipoxygenase, was used to examine the role of endogenous metabolites of arachidonic acid. Regardless of the agonist used, TIMP production by macrophages was inhibited 65% by indomethacin, synthesis of interstitial collagenase was reduced 70%, and expression of 92-kDa gelatinase was decreased 40%. In contrast, inhibition of leukotriene synthesis had no effect on metalloproteinase or TIMP production. The agonist-stimulated increase in TIMP and collagenase production was directly correlated to the cumulative prostaglandin E2 level induced by the agonist used. However, if response to an agonist was poor, the exogenous addition of prostaglandin E2 could not increase TIMP or collagenase production more than twofold, indicating an important permissive effect of the agonist on the regulation of each protein's expression. The mechanism of indomethacin inhibition of TIMP and collagenase production was studied by labeling the cells with [35S]-methionine and performing immunoprecipitation using specific antiserum. Indomethacin markedly inhibited the lipopolysaccharide-induced biosynthesis of both TIMP and collagenase. Northern analysis revealed parallel suppression of TIMP and collagenase steady-state mRNA levels by indomethacin, indicating pretranslational control. The regulation of inflammatory-cell TIMP and interstitial collagenase expression by prostaglandin E2 suggests that therapy inhibiting the cellular response to prostaglandins may be useful in cutaneous and systemic disease states involving macrophage-mediated connective-tissue destruction.
J Invest Dermatol 1995 Jan
PMID:Agonist-induced expression of tissue inhibitor of metalloproteinases and metalloproteinases by human macrophages is regulated by endogenous prostaglandin E2 synthesis. 779 41

To examine the effects of different wavelengths of ultraviolet (UV) radiation on tumor necrosis factor (TNF) production, we took advantage of mice carrying a chloramphenicol acetyl transferase (CAT) reporter transgene bearing the entire TNF promoter and 3'-untranslated region. Aside from constitutive expression in the thymus, CAT activity was detected only in locally UVB- or UVC-irradiated skin. After UVB irradiation, markedly greater amounts of CAT activity were traced to the dermis rather than the epidermis; by contrast, almost all CAT activity was localized to the epidermis after UVC irradiation. Fibroblasts have not been shown previously to express the TNF gene, i.e., the TNF gene is highly methylated and inaccessible to exogenous modulation in 3T3 fibroblasts. However, the present report reveals that cultured dermal fibroblasts are capable of producing both CAT and TNF in response to treatment in vitro with either UVB irradiation, UVC irradiation, or lipopolysaccharide. These findings indicate that dermal fibroblasts may serve not only as a target for but also as a source of TNF.
J Invest Dermatol 1995 Mar
PMID:Expression of the tumor necrosis factor gene by dermal fibroblasts in response to ultraviolet irradiation or lipopolysaccharide. 786 Sep 94

Nickel, cobalt and chromium are metals very often implicated in allergic contact dermatitis. In vivo, keratinocytes, which are the first target cells, can be directly activated to participate in the local reaction, especially through the expression of the membrane antigen ICAM-1, a ligand of the leucocyte antigen LFA-1, and the production of cytokines. Our aim was to assess the effects of sensitizing metal haptens (nickel, cobalt and chromium) compared with the toxic metal cadmium on the induction of ICAM-1 and the production of TNF alpha by epidermal cells. For this purpose, normal human keratinocytes obtained during plastic skin surgery were cultured in low-calcium defined medium (MCDB153) and the metals were used in non-toxic concentrations. Using FACS analysis, ICAM-1 expression was found to be induced only by nickel. This stimulation appeared as early as 24 h after stimulation. All the metals induced a low expression of TNF alpha detectable by immunocytochemistry correlating with the induction of the nuclear stress protein Hsp72 which is closely linked genetically with the TNF alpha locus. However, only Ni2+, Co2+ and Cr2+ induced a significant release of TNF alpha detectable by ELISA after 48 h stimulation. This secretion was lower than that observed with known stimulants such as lipopolysaccharide. These results indicate that the metals studied are able to induce an aggressive cellular effect, and that nickel, by its ICAM-1 induction, may play a major role in the keratinocyte activation state during allergic contact dermatitis.
Arch Dermatol Res 1994
PMID:Effect of various metals on intercellular adhesion molecule-1 expression and tumour necrosis factor alpha production by normal human keratinocytes. 786 60

The construction of an in vitro model allowed an investigation of the basic functions of immunocompetent cells after laser irradiation. Among low-energy laser sources, the helium-neon (He-Ne) laser, with a wavelength of 632.8 nm, has often been found to produce photobiological effects including evidence of interference with immunological functions. Previous experiments revealed an influence of He-Ne laser irradiation on concentrations of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) in supernatants of cultures of human peripheral blood mononuclear cells (PBMC) with increased cytokine concentrations after irradiation of 18.9 J/cm2 and decreased concentrations after irradiation of 37.8 J/cm2. Now, the mechanisms involved were studied. Results showed that cytokine production of cells stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or bacterial lipopolysaccharide (LPS) was altered significantly after laser irradiation but not after stimulation with staphylococcus aureus enterotoxin B (SEB). In situ hybridization of IFN-gamma mRNA producing PBMC revealed that the number of positive cells was modulated similarly. The results were identical in cultures of enriched monocytes (M phi) or enriched T cells. Cells of the human monocytic cell line Mono Mac 6 were also influenced after LPS stimulation, whereas constitutively IL-2-producing Jurkat cells were not influenced by laser irradiation at any energy density. Analysis of the IL-2 receptor (IL-2R) and intercellular adhesion molecule-1 (ICAM-1) expression in PBMC showed partial down-regulation of both receptors at 37.8 J/cm2, but only after stimulation with PHA.(ABSTRACT TRUNCATED AT 250 WORDS)
Exp Dermatol 1993 Mar
PMID:Helium-neon laser irradiation induces effects on cytokine production at the protein and the mRNA level. 790 41

The capacity of ultraviolet B (UVB) radiation to damage the cutaneous immune system has been extensively documented, and there is good reason to believe that UVB-induced damage is a critical, albeit permissive, factor in the development of sunlight-induced skin cancers. A summary of the evidence shows that acute, low-dose UVB protocols, which resemble quantitatively and qualitatively the manner in which human beings typically experience sun exposure, alter the cutaneous immune system in at least two important ways: they impair the induction of contact hypersensitivity to cutaneous antigens, and induce antigen-specific tolerance. In mice there is compelling evidence that immunogenetic factors dictate whether UVB radiation will impair contact hypersensitivity induction or not. The genetic loci that contain the relevant polymorphic alleles include tumor necrosis factor-alpha and lipopolysaccharide. Because the effects of UVB radiation on contact hypersensitivity induction are mimicked by intracutaneous injections of subinflammatory doses of tumor necrosis factor-alpha or cis-urocanic acid, the favored hypothesis to explain the mechanism of action of UVB radiation in UVB-susceptible individuals is that UVB-dependent transformation of trans- to cis-urocanic acid in the epidermis triggers the intracutaneous release of excess amounts of tumor necrosis factor-alpha. By transiently immobilizing Langerhans cells and other local antigen-presenting cells within the skin, the requirement that hapten be brought to the draining lymph node to sensitive naive hapten-specific T cells is not met, and contact hypersensitivity fails to develop. Because the UVB-susceptibility and UVB-resistance traits have also been demonstrated in human beings, the hypothesis is advanced that these traits are similarly under control of immunogenetic factors, and that a constellation of immune susceptibility genes contributes to the risk of developing sunlight-induced skin cancer. The cellular and molecular basis of UVB-induced tolerance is not as well described, but current evidence suggests that different mechanisms, and presumably different polymorphic genes, dictate whether tolerance will emerge after UVB exposure in mice. Because acute, low-dose UVB also induces tolerance in human beings, the immunogenetic factors that dictate tolerance of this type may also contribute to the risk of developing sunlight-induced skin cancer.
J Invest Dermatol 1994 Nov
PMID:Relationship between ultraviolet radiation-induced immunosuppression and carcinogenesis. 796 70


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