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)

These studies were done to examine the role of interleukin-4 (IL-4) in the generation of isotype specific antibody responses of mice to Pseudomonas aeruginosa lipopolysaccharide (PALPS) by neutralization of IL-4 in vivo using anti-IL-4 antibody (11B11). We found that the administration of anti-IL-4 antibody (11B11) 24 h before immunization with PALPS resulted in a decreased PALPS-specific antibody response for all isotypes examined (IgM, IgG1, IgG2a, IgG2b, IgG3). By contrast, we observed that the non-antigen-specific (polyclonal) IgM response of mice following treatment with 11B11 antibody and PALPS was increased while the polyclonal responses for the other isotypes were unaffected. When mice were given recombinant IL-10 at the time of immunization with PALPS there was a decrease in the PALPS-specific antibody response but an increase in the polyclonal IgM, IgG2a, IgG2b, IgG3 response whereas the polyclonal IgG1 response was decreased by a five-fold margin. The results of these studies suggest that both the antigen-specific and the polyclonal response can be influenced in a different manner by IL-4 or by IL-10.
 ...
PMID:Effects of IL-4 depletion on the antibody response to Pseudomonas aeruginosa lipopolysaccharide in mice. 824 45

We established a thyroglobulin (Tg)-specific, thyroiditis-inducing T-cell clone, B12G, from B6C3F1 mice by the immunization of mouse Tg with lipopolysaccharide (LPS) from Klebsiella strain LEN (O3:K1). B12G was Thy-1.2+, CD3+, CD4+, CD18+, and CD8-, and could transfer thyroiditis to recipient mice after in vitro stimulation with mouse or bovine Tg. Histological examination showed severe thyroiditis with predominant infiltrations of polymorphonuclear cells; few mononuclear cells were observed. B12G proliferated in response to bovine, mouse, porcine, and rat Tg in the presence of irradiated spleen cells, but did not respond to chicken or human Tg. H-2b, a low-responder haplotype of experimental autoimmune thyroiditis, governed the response of the clone to Tg. B12G produced interleukin-4 (IL-4) and IL-6, but not IL-2 or interferon-gamma (IFN-gamma), on stimulation with mouse Tg. These findings were different from characteristics of previously reported Tg-specific T-cell clones from high-responder mice in terms of epitope specificity and cytokine production pattern, raising the possibility that the specificities and functions of T cells involved in the development of autoimmune thyroiditis in low-responder mice differ from those in high responders.
 ...
PMID:Characterization of a thyroiditis-inducing thyroglobulin-specific T-cell clone restricted by the H-2 molecule of a low responder mouse strain. 828 21

To understand the differential role of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in the process of macrophage tumoricidal activation, we investigated the production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide in activated murine macrophages and the effects of those lymphokines on prostaglandin E2 (PGE2)-mediated down-regulation. IFN-gamma and IL-4 increased lipopolysaccharide (LPS)-induced TNF-alpha production by different mechanisms because IL-4, unlike IFN-gamma, failed to overcome the LPS-hyporesponsiveness in C3H/HeJ mice. Moreover, only IFN-gamma synergized with LPS to induce nitric oxide production and blocked eicosanoid-mediated down-regulation. These differential effects of IFN-gamma and IL-4 on the select efferent cytolytic activities may be the result of an altered or different signal transduction pathway. Because potentiation of protein kinase C (PKC) activity by IFN-gamma has been previously documented, we next studied the role of IFN-gamma and IL-4 in alteration of enzymatic activity of PKC. Two lymphokines caused translocation of PKC from cytosol to membrane with different levels, providing a biochemical basis for explaining how two lymphokines lead to different phenotypic responses. Although treatment of macrophages with IFN-gamma and IL-4 gave rise to a similar enhancing effect on macrophage TNF-alpha production, these two lymphokines appeared to differentially regulate the overall functional state of macrophages for tumour cell killing capability. Additionally, this differential regulation seems to be accomplished in part by different biochemical events.
 ...
PMID:Regulation of murine macrophage function by IL-4: IL-4 and IFN-gamma differentially regulate macrophage tumoricidal activation. 830 12

Stimulation of B lymphocytes with a combination of lipopolysaccharide (LPS) and interleukin-4 (IL-4) induces germline transcription of and subsequent switching to the epsilon heavy chain constant region (C epsilon) gene. Mature germline C epsilon transcripts contain a non-coding exon (I epsilon exon) spliced to the C epsilon exons. To distinguish between the potential roles of germline transcription and those of germline transcripts in regulating the class switch process, we replaced the LPS- and IL-4-inducible I epsilon promoter and exon in ES cells with an LPS-inducible E mu enhancer/VH promoter expression cassette. Wildtype, heterozygous or homozygous mutant ES cells were injected into RAG-2 deficient blastocysts to generate somatic chimeras in which all B cells derived from ES cells. In contrast to normal B cells, heterozygous and homozygous mutant B cells had substantial transcription through the epsilon switch recombination region (S epsilon) following treatment with LPS alone and, under these conditions, both underwent low level switching (10- to 100-fold less than wildtype cells stimulated with LPS + IL-4) to IgE production. Heterozygous mutant cells underwent switching to IgE at essentially wildtype levels when stimulated with LPS and IL-4. However, homozygous mutant cells still showed extremely low levels of switching to IgE upon LPS and IL-4 stimulation. Analyses of hybridomas from heterozygous mutants indicated that the mutation is cis-acting and normal switching to other isotypes indicated that it is specific for IgE. Thus transcription per se generates low levels of class switch recombination in the absence of I region sequences. However, we demonstrate for the first time that, for optimal efficiency, the process requires the presence of the intact I region and/or I region promoter in cis, implicating factors beyond transcription through the S region in the regulation of class switching.
 ...
PMID:S region transcription per se promotes basal IgE class switch recombination but additional factors regulate the efficiency of the process. 831 11

Apoptosis or programmed cell death is a physiological form of cell suicide that is profoundly influenced by the extracellular microenvironment. Apoptosis is characterized by a cascade of genetic and biochemical events that cause cell shrinkage, condensation of cytoplasmic and nuclear material, cleavage of chromosomal DNA into oligonucleosomesized (approximately 200 bp) fragments, and enhanced recognition of the dying cell by phagocytes. Apoptosis differs fundamentally from necrosis, the pathological form of cell death, in which the cell swells and lyses. The capacity to selectively induce apoptosis in leukocytes might be an important physiological mechanism for controlling accumulation of these cells in inflammatory lesions. In this paper, we review our data on apoptosis in human monocytes, cells which contribute both to the persistence and resolution of chronic inflammation. Apoptosis can be initiated when monocytes are cultured in the absence of appropriate exogenous stimulation. For example, addition of chemotactic factors is insufficient to block apoptosis. However, apoptosis in monocytes can be inhibited by adherence in the presence of serum, by microbial products such as lipopolysaccharide, or by certain pro-inflammatory cytokines, such as interleukin 1 and tumor necrosis factor-alpha. Cytokines derived from type 1 helper T cells (e.g., interferon-gamma) inhibit apoptosis whereas those derived from type 2 helper T cells (e.g., interleukin-4) enhance apoptosis in activated monocytes. Thus, cytokines derived from monocytes as well as T cells modulate apoptosis, implicating both autocrine and paracrine regulatory circuits in monocyte survival. The capacity to therapeutically regulate monocyte apoptosis promises to have tremendous value in promoting rapid healing or reducing the immunopathogenesis of chronic inflammation.
 ...
PMID:Apoptosis in human monocytes: possible role in chronic inflammatory diseases. 831 69

Endothelial cells (EC) may regulate both local and systemic aspects of inflammation through the synthesis of cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-6 (IL-6). EC are known to synthesize these cytokines in response to interleukin-1 (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). In this paper, we illustrate the effect of interleukin-4 (IL-4) in reducing the synthesis of GM-CSF by EC stimulated with IL-1 alpha, TNF-alpha, or LPS. This is compared with the previously reported strong synergy between IL-4 and IL-1 alpha, TNF-alpha, or LPS in the synthesis of IL-6 by EC. No clear effect of IL-4 was seen in the synthesis of G-CSF or M-CSF. The range of concentrations of IL-4 at which these effects were seen was identical for both reduced GM-CSF synthesis and increased IL-6 synthesis. The effect of IL-4 on IL-6 synthesis was seen by 4 h of treatment, while that on GM-CSF was apparent between 4 and 8 h. It is suggested that these contrasting effects of IL-4 may reflect a biological role for this cytokine in the regulation of leukocytosis and the acute phase response.
 ...
PMID:Contrasting effects of interleukin-4 on colony-stimulating factor and interleukin-6 synthesis by vascular endothelial cells. 832 81

Mononuclear phagocytes are essential cellular mediators of both acute and chronic inflammatory responses. In addition to producing substances that mediate tissue injury directly, such as proteolytic enzymes and oxygen radical species, mononuclear phagocytes can secrete proteins involved in the activation and recruitment of inflammatory cells. One of the major inducible polypeptides secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1). Native MIP-1 is a protein with leukocyte chemotactic and stimulatory activity. MIP-1 consists of two highly homologous peptides, MIP-1 alpha and MIP-1 beta. We now characterize the expression of MIP-1 alpha from human peripheral blood monocytes (PBM) and identify the T-lymphocyte product interleukin-4 (IL-4) as an important regulator of MIP-1 alpha expression from PBM. In initial experiments, we demonstrated the production of MIP-1 alpha from lipopolysaccharide (LPS)-, interleukin-1 (IL-1)-, and phytohemagglutinin (PHA)-stimulated PBM. IL-4 inhibited the production of MIP-1 alpha from LPS-, IL-1-, and PHA-challenged PBM by 63, 81, and 88%, respectively. The suppressive effects of IL-4 were operative at the level of MIP-1 alpha mRNA, which was reduced in a dose-dependent fashion by IL-4. The suppression of MIP-1 alpha mRNA by IL-4 was observed within a narrow temporal window and was dependent upon the de novo synthesis of a protein intermediate. As determined by mRNA stability studies, IL-4 decreased steady-state levels of MIP-1 alpha mRNA, in part, by accelerating MIP-1 alpha mRNA decay.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Gene expression of macrophage inflammatory protein-1 alpha from human blood monocytes and alveolar macrophages is inhibited by interleukin-4. 833 86

The capacity of exogenous interleukin-4 (IL-4) and IL-5 to augment the antigen-specific senescent Peyer's patch (PP), lamina propria (LP), and mesenteric lymph nodes (MLN) B cells was investigated in the present studies. CTx-primed lymphocytes in the PP, LP, and MLN were obtained from 4-and 24-month old C57BL/6J male mice, 14 days after oral immunization with cholera toxin (CTx). Cells were cultured optimally for 4 days either alone, with lipopolysaccharide (LPS), with LPS plus recombinant IL-4 or IL-5, or with LPS plus IL-4 or IL-5 plus monoclonal antibodies specific for the respective interleukin. Culture supernantants were tested for IgA and IgG anti-CTx antibodies by an ELISA assay. The data indicated impaired antibody responses of aged PP and MLN B cells by the lack of LPS plus IL-4 induced enhancement of anti-CTx IgG antibody production as compared with the young group. For anti-CTx IgA production, aged LP and MLN B cells did not respond equally as well to LPS plus IL-5 stimulation as the young group. In contrast, aged PP B cells responded equally as well by anti-CTx IgA production to LPS plus IL-5 stimulation as the young group. Both anti-IL-4 and anti-IL-5 Mabs blocked the respective IL-4 and IL-5-induced enhancement of antigen-specific IgG or IgA antibody production. The findings suggest a regional dichotomy of IL-5 induced enhancement of aged IgA-producing B cells specific for CTx in the Peyer's patches, mesenteric lymph nodes, and lamina propria.
 ...
PMID:Regional dichotomy of interleukin-4 and -5 regulation of senescent B cell responses specific for cholera toxin in Peyer's patches, lamina propria, and mesenteric lymph nodes. 834 71

The effect of interleukin-4 (IL-4) on the proliferation and differentiation of myeloid leukemic cell lines was studied in vitro. A culture of murine myeloid cell line, M1, with lipopolysaccharide (LPS) from Escherichia coli, induced differentiation into macrophages that expressed Fc receptors and phagocytic activity. IL-4 did not induce the differentiation of M1 cells but inhibited the differentiation of M1 cells induced with LPS. On the other hand, LPS arrested the proliferation of M1 cells. IL-4 had no effect on the proliferation of M1 cells but restored the LPS-induced arrest of the proliferation of M1 cells. IL-1, IL-6 and tumor necrosis factor alpha (TNF-alpha) also induced the differentiation of M1 cells into macrophages and arrested proliferation. IL-4 suppressed the IL-1-, IL-6-, and TNF-induced differentiation of M1 cells and restored the arrested proliferation with IL-1, IL-6, and TNF. Similar results were obtained with human myeloid cell line HL60. These results suggest that IL-4 has a suppressive effect on the differentiation of myeloid cells into macrophages.
 ...
PMID:Suppressive effect of interleukin-4 on the differentiation of M1 and HL60 myeloid leukemic cells. 836 May 93

We studied the effect of interleukin-4 (IL-4) on the lipopolysaccharide (LPS) induction of two immediate early genes c-fos and c-jun. These genes encode proteins that form the dimeric complex activator protein-1 (AP-1), which is active as a transcriptional factor. Maximal accumulation of either c-fos and c-jun messenger RNA (mRNA) occurred 30 minutes after LPS addition. When cells were treated with IL-4 for 5 hours before LPS activation, both the c-fos and the c-jun mRNA expression was decreased. The inhibition of c-fos and c-jun expression by IL-4 in LPS-treated cells was shown to be due to a lower transcription rate of the c-fos and c-jun genes. IL-4 did not affect the stability of the c-fos and c-jun transcripts. Finally, using electrophoretic mobility shift assays, evidence was obtained that IL-4 inhibits LPS-induced expression of AP-1 protein. These data indicate that IL-4 suppresses the induction of transcription factors in human activated monocytes.
 ...
PMID:Interleukin-4 inhibits the lipopolysaccharide-induced expression of c-jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes. 842 59


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