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 acute monocytic leukemia cell line THP-1 secretes predominantly IL-1 beta after treatment with bacterial lipopolysaccharide and tumour promoting phorbol ester (PMA). IL-1 alpha is also secreted, but represents less than 10% of the total IL-1 activity. This differential is reflected at the level of mRNA as IL-1 beta mRNA is more abundant than IL-1 alpha mRNA. Studies of transcription in isolated nuclei however indicate that each gene is transcribed at a similar rate, suggesting that post-transcriptional mechanisms regulate the relative abundance of IL-1 alpha and IL-1 beta mRNA. Measurement of RNA half life after addition of alpha-amanitin (an inhibitor of RNA polymerase II) indicate that IL-1 alpha mRNA is not as stable as IL-1 beta mRNA suggesting one mechanism for the different relative levels of RNA.
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PMID:Post-transcriptional control of IL-1 gene expression in the acute monocytic leukemia line THP-1. 326 53

In the present study we investigated the capability of human epidermal cells to generate granulocyte-activating mediators (GRAM). It could be shown that human epidermal cells as well as an epidermoid carcinoma cell line (A431) produce an epidermal cell-derived granulocyte-activating mediator (EC-GRAM) which stimulates human granulocytes to release significant levels of toxic oxygen radicals as measured by a lucigenin-dependent chemiluminescence (CL). For further characterization of EC-GRAM the A431 cell line was used. Supernatants of A431 cells usually contained maximal EC-GRAM levels within 24 h of incubation. Factor production was enhanced by bacterial lipopolysaccharide (LPS), but not by silica particles and PHA. Moreover, freeze-thaw lysates of A431 cells and extracts of heat-separated human epidermis contained significant levels of EC-GRAM. Preincubation of granulocytes with EC-GRAM resulted in an enhanced response to subsequent stimulation with the chemotactic peptide f-met-phe. In contrast EC-GRAM did not affect the response to PMA or zymosan particles. However, EC-GRAM treated granulocytes were unresponsive to restimulation with EC-GRAM. Upon high performance liquid chromatography (HPLC) gel filtration EC-GRAM eluted within two major peaks exhibiting a molecular weight of 17 kD and 44 kD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte-activating mediators (GRAM). II. Generation by human epidermal cells--relation to GM-CSF. 332 74

C3H/HeJ mice are hyporesponsive to the biologic effects of bacterial lipopolysaccharide (LPS), and their splenic B cells do not proliferate after exposure to LPS. The molecular basis of this hyporesponsiveness is unknown but it may result from defective membrane signal transduction after LPS binding. To examine this possibility, we added bioactive compounds in combination with LPS to C3H/HeJ B cell cultures in order to bypass the putative defect. The addition of PMA, monensin, or ionomycin, either alone or in combination, had no effect on C3H/HeJ B cell responses to LPS. In contrast, the addition of trypsin together with LPS resulted in a partial restoration of the proliferative response in C3H/HeJ splenic B lymphocytes. The maximal C3H/HeJ B cell response varied from 25 to 60% of the C3Heb/FeJ (LPS responder) B cell response. The trypsin-mediated enhancement of the LPS response was abrogated by pretreatment of the trypsin with the trypsin inhibitors DFP or TLCK. Pretreatment of the LPS with polymyxin B, which blocks lipid A-dependent reactions, also abrogated the trypsin effect. Because the C3H/HeJ B cell responds to all other B cell mitogens, we suggest that the defect is in an LPS-specific step and that the action of trypsin results in the restoration of the missing signal. At the present time the identity of this signal is not known, but the experiments described in this report provide a unique model to elucidate the basis of LPS hyporesponsiveness in splenic B cells from C3H/HeJ mice.
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PMID:Partial restoration of the lipopolysaccharide-induced proliferative response in splenic B cells from C3H/HeJ mice. 348 72

A factor produced by lipopolysaccharide-stimulated human monocytes, monocyte-derived eosinophil cytotoxicity-enhancing factor (M-ECEF), increases the ability of human eosinophils to kill larvae of Schistosoma mansoni. In order to purify this monokine, a continuous cell line was sought as a generator of source material. It was found that high titers of an ECEF-like activity could be obtained from the U937 cell line cultured in serum-free medium. Production of this activity was optimal when cells were cultured with PMA for 2 days and were further treated with LPS for 2 days. PMA and LPS alone did not enhance eosinophil cytotoxicity and could be separated completely from U937-ECEF activity by reversed-phase HPLC. Thus, the activity was not due to carry-over of these two stimuli. U937-ECEF was compared with M-ECEF by a number of analytical methods. ECEF from both sources was resistant to several denaturing treatments but was sensitive to proteases or to reduction and alkylation. U937-ECEF exhibited activity profiles similar, if not identical, to those of M-ECEF when subjected to molecular sizing HPLC in the presence of 8 M urea, isoelectric focusing, and reversed-phase HPLC. The activity has apparent m.w. of 17,000 and 32,000, isoelectric points ranging from 3.8 to 5.1, and one or more reversed-phase HPLC retention times, depending on the method of sample preparation. These results demonstrate certain physical characteristics of M-ECEF, show that the U937 cell line is an appropriate source for the purification of M-ECEF, and provide information that will allow the design of a purification strategy. Although it appears that tumor necrosis factor (TNF) or a TNF-like molecule is a component of M-ECEF, a major component of M-ECEF is different from TNF as judged by the 1) physical characteristics of M-ECEF, 2) low direct toxicity of M-ECEF to L929 cells, 3) comparative stability of M-ECEF to heat treatment, and 4) inability of an anti-TNF monoclonal antibody to remove M-ECEF activity.
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PMID:Characterization of a factor from the U937 cell line that enhances the toxicity of human eosinophils to Schistosoma mansoni larvae. 349 78

Peritoneal macrophage ganglioside patterns and ganglioside sialic acid content were compared for two congenic strains of mice having differing responses to bacterial lipopolysaccharide. Resident macrophage ganglioside patterns from C3H/HeJ mice (endotoxin hyporesponsive) and C3H/HeN mice (endotoxin responsive) were similar. Macrophages elicited with phenol-extracted or butanol-extracted endotoxin showed distinctly more complex ganglioside patterns in C3H/HeN mice. C3H/HeJ macrophages showed distinct, but less complex changes when elicited with butanol-extracted endotoxin. As expected, there were minimal alterations induced by phenol-extracted endotoxin in the C3H/HeJ patterns. When injected with whole killed E. coli, both strains of mice exhibited complex ganglioside patterns; however, there were relative differences in the quantities of multiple gangliosides. Differences in ganglioside patterns were mirrored in the relative ratios of N-acetyl- to N-glycolylneuraminic acid. When macrophages were activated by administration of either endotoxin preparation, macrophage gangliosides from C3H/HeN mice always contained a higher proportion of N-acetylneuraminic acid compared with C3H/HeJ macrophage gangliosides. Oxidative metabolism of the macrophage populations was assessed by PMA-induced H2O2 release. This indicated that endotoxin activation produced an increase in PMA-induced H2O2 release as well as a shift of sialic acid class from the N-glycolyl type to the N-acetyl type. However, no direct correlation could be made between ganglioside composition, sialic acid content, and macrophage function. These data indicate that both ganglioside composition and sialic acid composition of macrophages are profoundly altered with endotoxin activation. The data further indicate that under conditions which C3H/HeJ mice respond to Gram-negative bacteria, their macrophage ganglioside patterns still differ from normal mice.
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PMID:Ganglioside expression in macrophages from endotoxin responder and nonresponder mice. 353 27

1 The mechanisms by which agents modulate the induction of kinin B1-receptors were investigated by studying the effects of kinins in vitro, by use of the rabbit isolated aorta, and in vivo by measuring the blood pressure of anaesthetized rabbits. 2 The contractile response of the rabbit isolated aorta to kinins increased in a time-dependent manner in vitro. This effect was abolished by continuous exposure to the protein synthesis inhibitor cycloheximide (71 microM). 3 Several substances were found to increase specifically the rate of sensitization to des-Arg9-bradykinin (des-Arg9-Bk), when applied continuously in vitro to tissues isolated from normal animals: bacterial lipopolysaccharide (LPS; 1 micrograms ml-1), muramyl-dipeptide (MDP; 2 micrograms ml-1), phorbol myristate acetate (PMA; 320 nM), epidermal growth factor (EGF; 100 ng ml-1) and endothelial cell growth factor (150 micrograms ml-1). 4 The protease inhibitors phenylmethylsulphonyl fluoride and aprotinin, a non-adjuvant isomer of MDP, rabbit purified leukocyte interferon, fibroblast growth factor and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) did not have this effect. 5. It has been demonstrated that LPS induces B1-receptors in rabbits enabling des-Arg9-Bk to act as a hypotensive agent. In these experiments neutropenia induced by nitrogen mustard, did not prevent the in vivo effect of LPS. MDP (300 micrograms) and PMA (100 micrograms) were also found to induce a state of responsiveness to des-Arg9-Bk in vivo. FMLP (1 mg i.v.) induced a temporary decrease in blood neutrophil counts but had no effect on the induction of responses to des-Arg9-Bk. 6. The development of responses mediated by the B,-receptor in the two experimental systems seems to be unrelated to the activation of neutrophil leukocytes, but may be related to the activation of tissue macrophages. Approximately 3% of cultured adherent cells derived from rabbit aorta strips following protease digestion were stained for non-specific esterase, supporting such a possibility.
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PMID:Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. 367 93

Mouse thymocytes and spleen cells from unprimed C57BL/6 donors generate broadly reactive cytotoxic cells during 5 days of culture in vitro with polyinosinic acid (5') (poly(I] and/or supernatant from PMA-treated EL4 leukemia cells which contains interleukin 2 (IL-2) activity. We refer here to such cytotoxic cells as "supplement-induced cytotoxic cells" or SICC. Thymocytes are dependent on the supernatant factor(s), whereas spleen cells are usually stimulated by poly(I) alone. Polyinosinic acid acts synergistically with supernatant factor(s) to stimulate generation of SICC by both thymocytes (SICC-T) and spleen cells (SICC-S) when the IL-2 activity of the supernatant is inadequate alone. SICC can be generated by both splenocytes and thymocytes in medium supplemented with fetal calf serum or syngeneic plasma. SICC are active in 4 hr 51Cr-release tests against syngeneic, allogeneic, and xenogeneic tumors but not against lipopolysaccharide-induced lymphoblasts. Embryonic fibroblasts, too, are sensitive to SICC generated by thymocytes. In complement-dependent depletion tests, cytotoxic activity is partially sensitive (SICC-T) or fully sensitive (SICC-S) to anti-Thy-1 and -H-2 but not to anti-Lyt-1, -Lyt-2, or -asialo GM1.
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PMID:Supplement-induced cytotoxic cells (SICC) generated from mouse thymus or spleen cells cultured in the presence of interleukin 2 and/or polyinosinic acid. 660 5

Spleen cells of diabetes-prone BB Wistar rats were found to generate excessively low proliferative responses, and interleukin 2 (IL-2) levels in response to T-dependent mitogens. This abnormality was not due solely to abnormal T cell numbers since: (a) addition of BB spleen cells of BB splenic macrophages to normal major histocompatibility complex (MHC)-matched Wistar Furth (WF) spleen cells resulted in severe suppression of concanavalin A (Con A)-, phytohemagglutinin (PHA)-, and pokeweed mitogen (PWM)-mediated proliferation, and IL-2 production; (b) macrophage depletion from BB spleen cells, but not B cell or T cell depletion, removed completely the suppressive effects of BB cells on WF cells; (c) macrophage depletion greatly enhanced the response of BB lymphocytes to T-dependent mitogens. Although suppressor macrophages could also be found in the spleen of WF control rats they were present in much smaller numbers than in the spleen of BB rats. The suppressive effect of BB macrophages was partially reduced by addition of the prostaglandin synthetase inhibitor indomethacin to cultures. Furthermore, indomethacin (but not catalase or PMA) considerably augmented IL-2 secretion of Con A-stimulated BB spleen cells, but had little effect on WF spleen cells. In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production. While IL-2 secretion was severely depressed in BB rats unstimulated and lipopolysaccharide (LPS)-stimulated IL-1 secretion by splenic macrophages was normal. BB macrophages did not inactivate IL-2. Low IL-2 production and macrophage-mediated suppression were features of all BB rats tested.
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PMID:Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages. 660 15

The spontaneous and induced interferon (IFN) production in whole blood cultures was examined in 45 psychiatric inpatients and in 65 normal controls. Among inpatients there were 32 who were chronic schizophrenics (14 women, 18 men) and 13 who were severely depressed (11 women, 2 men). The analysis of the pooled results of assays in the heterogeneous population showed that leukocytes of the psychiatric patients produced significantly lower levels of IFN after stimulation with virus (NDV), lipopolysaccharide (LPS), and IFN spontaneously released without the inducers that control cells. In contrast, there was no difference between the psychiatric patients and controls in IFN response to phytohemagglutinin and phorbol myristate acetate (PHA + PMA). The results apparently confirmed observations made by Moises et al (1985) and Katila et al (1989). We have also tested our hypothesis that the statistics may mask the individual pattern of IFN response related to the specific psychiatric diagnosis, however. In fact, in the group of chronic schizophrenics we have found either high or low responders to all IFN inducers (NDV, PHA + PMA and LPS). Furthermore, the patients with high IFN response had dominant positive symptoms of schizophrenia (delusions, hallucinations, bizarre behavior and thought disorder). Whereas, in the patients with low IFN response the negative symptoms prevailed (asociality or withdrawal, flat affect, attention impairment, abolition or apathy). In plasma samples of schizophrenics, factors were detected that transferred a hypersensitivity to the IFN inducers to normal donor leukocytes. For instance, in leukocytes cultured in the presence of plasma from schizophrenics, there were 71% of high IFN responders after stimulation with NDV, versus 26% of high IFN responders in the presence of plasma from normal controls. We suggest that the factors may belong to the class of opioid peptides, which interact with the production of cytokines including IFNs.
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PMID:Interferon responses in schizophrenia and major depressive disorders. 751 91

This study describes the expression characteristics of E-selectin molecules using immunogold histochemical techniques on cultured human umbilical vein endothelial cells (HUVEC). The expression of E-selectin was induced by tumour necrosis factor-alpha (TNF-alpha, 300 U/ml), phorbol ester (PMA, 10 ng/ml) and bacterial lipopolysaccharide (LPS, 4 micrograms/ml). No expression was demonstrated on control cells. Using the silver-enhanced colloidal gold-labelling technique, at the light microscopical level, HUVEC could be distinctively subdivided into three staining types. The cell labelling index, expressed as the number of 'positively' stained cells as a proportion of all viewed cells was the highest in the LPS group. For transmission electron microscopy (TEM) the preembedding immunocytochemical staining method and embedding in epoxy resin (Agar 100) according to standard procedures was used. In TEM gold particles were localized in close association with the apical plasma membrane, as well as on the surface of microvillus-like projections (the latter by TNF-alpha group). For high resolution scanning electron microscopy (HR-SEM) the secondary (SEI) and the backscattered electron imaging (BEI) modes were used. Gold particles were randomly distributed over the whole cell surface, although they appeared to be denser in the perinuclear zone. The quantitative evaluation on SE and BE viewing (the number of gold particles per cell area in microns 2) demonstrated the highest density of labelling in the LPS-treated group, but there was only a significant difference between LPS and TNF-alpha groups (P < 0.01, t-test). Furthermore, the ultrastructural studies indicated that treatment with substances which up-regulate E-selectin expression was not related to toxic cell damage or significant alterations of cellular ultrastructure.
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PMID:Application of immunogold labelling for light and electron microscopic localization of endothelial leukocyte adhesion molecule 1 (ELAM-1) on cultured human endothelial cells. 752 Aug 16


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