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)

Antigens and infectious agents that stimulate interferon alpha(IFN-alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN-alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells.
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PMID:Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice. 194 Jul 96

Murine B cells stimulated with lipopolysaccharide (LPS) and interleukin (IL) 4 produce IgG1 and IgE, but synthesize IgG2a when stimulated with LPS and interferon-gamma. The cytokines, however, that regulate immunoglobulin (Ig) synthesis induced in normal B cells under antigen-driven major histocompatibility complex (MHC)-restricted conditions in the absence of potent B cell mitogens have not been fully elucidated. We and others have shown that under cognate MHC-restricted conditions, CD4+ T cell clones of the TH1 subset, which produce IL 2 and interferon-gamma, and T cell clones of the TH2 subset, which produce IL 4 and IL 5, are both capable of inducing anti-trinitrophenyl IgG plaque-forming cells. In this report we have examined in further detail the cytokine requirements for the induction of Ig synthesis in B cells cultured directly with TH1 and TH2 T cell clones. Using (a) TH2 clones that varied in the amount of IL 5 secreted, (b) a neutralizing monoclonal antibody against IL 5 and (c) T cell clones pretreated with cyclosporin A to inhibit cytokine secretion, we found that IL 5 was essential for induction of IgG1 synthesis by TH2 but not TH1 T cells. Although we demonstrated that IL 2 could actually up-regulate the synthesis of IL 5 by TH2 clones, the induction of IgG synthesis by TH2 clones was entirely independent of IL 2. In contrast, induction of IgG1 synthesis by TH1 clones was absolutely dependent upon the presence of IL 2 and was not affected by the presence of IL 5. Thus, these studies demonstrate the idea that at least two independent pathways exist for the induction of IgG1 synthesis, and that one of these pathways is IL 4/IL 5 dependent and the other IL 2 dependent.
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PMID:Induction of antibody synthesis by CD4+ T cells: IL 5 is essential for induction of antigen-specific antibody responses by TH2 but not TH1 clones. 197 8

In 31 adult patients with atopic dermatitis, the capacity to secrete interleukin-1 (IL-1) from peripheral blood mononuclear cells and from purified monocytes was investigated following stimulation with lipopolysaccharide. We also measured soluble interleukin-2 receptor levels (sIL-2R) and CD-8 receptor in serum from some of the patients in order to estimate the degree of lymphocyte stimulation in vivo. We observed that purified monocytes from patients with atopic dermatitis released more IL-1 than unseparated blood mononuclear cells did and also had significantly greater IL-1 activity than non-atopic donors. Addition of histamine in concentrations of 10(-7) to 10(-4) M did not suppress, but rather augmented the IL-1 activity release. An increased monocyte-IL-1 release could lead to increased T lymphocyte activity. We observed that 60% of the patients had increased sIL-2R concentrations in serum. There was no correlation between serum IgE and sIL-2R. Our observations indicate that monocytes in atopic dermatitis patients release increased quantities of IL-1, supporting an augmented T lymphocyte activation in the patients.
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PMID:Interleukin-1 release from peripheral blood monocytes and soluble interleukin-2 and CD8 receptors in serum from patients with atopic dermatitis. 198 Sep 72

P815, a transformed mouse mastocytoma cell line, produced and released cytotoxic factors after stimulation with phorbol 12-myristate 13-acetate (PMA), but not with lipopolysaccharide (LPS), calcium ionophore A23187 and IgE receptor triggering. The cytotoxic activity was reduced 60% by antibodies to mouse tumour necrosis factor (TNF). In addition, we demonstrated that TNF mRNA was already expressed under normal culture conditions and that it increased after stimulation with PMA. Although it was unknown whether factors other than TNF were lymphotoxin or some other unknown factors, it has been suggested that mast cells have cytotoxic activity, and that they contribute to inflammatory response through the release of TNF, which has a wide range of biological activity.
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PMID:Production of tumour necrosis factor by mastocytoma P815 cells. 210 86

This study evaluated the gene expression of tumour necrosis factor (TNF) and the molecular weight of the cytotoxic factor in a subline of a rat basophilic leukaemia cell line, RBL-2H3. After IgE receptor triggering with a specific antigen that was associated with histamine release, cytotoxic activity in the cell lysates and supernatants increased for 2 hr during the culture of RBL-2H3 cells. Furthermore, calcium ionophore A23187 could induce release of histamine and cytotoxic activity from RBL-2H3 cells. However, compound 48/80, lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) were unable to induce the release of either histamine or cytotoxic activity from the cells. These data suggested that, at least in part, there was a common pathway in histamine release and production of cytotoxic activity. A protein synthesis inhibitor, cycloheximide, did not affect histamine release, but inhibited the induction of cytotoxic activity. This cytotoxic activity from RBL-2H3 cells was completely neutralized by anti-mouse TNF rabbit serum. With Northern blot analysis, mouse TNF cDNA probe could hybridize with RNA isolated from RBL-2H3 cells. TNF mRNA was induced as early as 1 hr after stimulation with specific antigen and decreased by 4 hr. Moreover, the molecular weight (MW) of the released cytotoxic factor from RBL-2H3 cells triggered with IgE receptors was approximately 17,000 by SDS-PAGE, which was compatible to that of TNF. Thus, it is concluded that the gene expression and production of TNF occurred in RBL-2H3 cells after IgE receptor triggering in association with histamine release, suggesting that TNF produced by basophils and mast cells may play an important role in allergic reaction through its wide range of biological activity.
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PMID:Gene expression and production of tumour necrosis factor by a rat basophilic leukaemia cell line (RBL-2H3) with IgE receptor triggering. 214 21

Anti-2,4,6-trinitrophenyl (TNP) IgE antibody response was elicited by stimulating TNP-keyhole limpet hemocyanin-primed murine spleen cells with the same antigen in vitro. The released anti-TNP IgE was assayed by antigen- and isotype-specific enzyme immunoassay developed in our laboratory. When prostaglandin E2 (PGE2) was added to the lymphocyte culture at 10(-7) M, anti-TNP IgE response was augmented two- to fourfold. Interestingly, PGE2 did not affect the production of anti-TNP antibodies belonging to other isotypes including IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA. Moreover, PGE2 showed neither enhancing nor interleukin 4-replacing activities in the polyclonal IgE response by B cells stimulated with lipopolysaccharide and interleukin 4. When endogenous prostaglandin synthesis was inhibited by 10(-6) M indomethacin, the anti-TNP IgE response, but not the corresponding IgG response, was suppressed by 30%-60%. These results suggest a potential role of PGE2 in the up-regulation of the antigen-specific IgE response.
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PMID:Prostaglandin E2 as a selective stimulator of antigen-specific IgE response in murine lymphocytes. 225 88

In vitro IgE synthesis by lymphoid cells was studied during the course of infection of mice with Nippostrongylus brasiliensis. The studies involved inbred strains of mice which had been shown to be high IgE responders (A.CA, B10.M), or non-responders (Balb/c, B10.D2) to parasite antigen. In addition, F1 hybrids of low and high responders and irradiated non-responders were studied. Infection with N. brasiliensis led to an increase in IgE synthesis in vitro which was most pronounced during reinfection of mice. Addition of mitogens e.g. pokeweed mitogen (PWM), lipopolysaccharide (LPS), concanavalin A (ConA) to the cultures induced enhancement, suppression or had no effect on IgE synthesis. Addition of N. brasiliensis homogenate or worm culture supernatant led to a fluctuating pattern of IgE synthesis. No correlation was found between lymphocyte proliferative response to mitogen and worm antigens and IgE synthesis. Our data suggest, that PWM is more likely to enhance IgE synthesis in vitro than LPS or ConA. An enhancement is more easily observed with the cells of non-infected animals or during the early phase of infection or reinfection. The mitogen-induced increase in IgE synthesis did not exceed the values obtained during infection or reinfection.
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PMID:IgE synthesis in vitro during infection of mice with the nematode Nippostrongylus brasiliensis: effects of mitogens and antigens. 241 41

The regulation of the subclass of immunoglobulin secreted by B cells has been studied in vitro in polyclonal systems using mitogens, such as lipopolysaccharide (LPS), to bypass the requirement for cognate interaction between antigen-specific T and B cells. In these systems, interleukin-(IL)-4 induces the secretion of IgG1 (ref. 1) and IgE (ref. 2); IL-5 enhances the secretion of IgA, and interferon-gamma (IFN-gamma) enhances the secretion of IgG2a (ref. 5). Clones of murine TH cells can be divided into two subsets, TH1 and TH2 (ref. 6). Both subsets synthesize IL-3 and granulocyte-monocyte colony-stimulating factor (GM-CSF), but only TH1 clones produce IL-2, IFN-gamma, and lymphotoxin (LT) and TH2 clones produce IL-4 and IL-5 (ref. 7). We have examined the role of clones of antigen-specific TH1 and TH2 cells in the regulation of the subclasses of IgG antibody secreted by antigen-specific B cells. Our results show that both types of TH cells induce the secretion of IgM and IgG3, whereas clones of TH1 and TH2 cells specifically induce antigen-specific B cells to secrete IgG2a and IgG1, respectively. We also demonstrate that regulation of commitment to the secretion of a particular IgG isotype occurs in two distinct stages: cognate interaction between T and B cells and interaction between T-cell-derived lymphokines and B cells.
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PMID:Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. 245 66

Immunoglobulin heavy-chain switching is effected by a DNA recombination event that replaces the C mu gene with one of the other heavy-chain constant-region (CH) genes located 3' to the C mu gene. How the specificity of this event is controlled is unknown. However, it has been shown that IgM+ cells capable of switching to specific isotypes have the corresponding unrearranged CH genes in an accessible or active chromatin state, as demonstrated by the fact that these specific CH genes are hypomethylated and are transcriptionally active. We now report that the RNAs transcribed from specific unrearranged CH genes are induced prior to switching under conditions that promote switching to these specific CH genes. For example, we find that bacterial lipopolysaccharide, which induces the IgM+ cell line I.29 mu to switch to IgA, induces transcripts from the germ-line C alpha gene(s) in I.29 mu cells prior to switch recombination. Two preparations of T-cell lymphokines (recombinant interleukin 4 and supernatant from the T-cell line 2.19, which contains interleukins 4 and 5) that promote switching to specific isotypes by lipopolysaccharide-treated spleen cells induce transcripts from the corresponding germ-line CH genes prior to expression of the new isotypes. For example, interleukin 4, which appears to be necessary for switching to IgE in vitro and in vivo, induces within 2 days large increases in germ-line C epsilon transcripts in lipopolysaccharide-treated spleen cells and in I.29 mu cells. The most straightforward interpretation of our data is that these lymphokines direct switching to specific isotypes by activating specific CH genes, making them accessible to the putative switch recombinase.
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PMID:Immunoglobulin heavy-chain switching may be directed by prior induction of transcripts from constant-region genes. 245 14

Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line gamma 1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon gamma. IL-4 alone is capable of inducing the expression of germ-line gamma 1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional gamma 1 mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the gamma 1 constant-region exon(s). These data strongly support the "accessibility" model for the regulation of isotype switching and suggest that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.
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PMID:Synthesis of germ-line gamma 1 immunoglobulin heavy-chain transcripts in resting B cells: induction by interleukin 4 and inhibition by interferon gamma. 249 37


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