Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to investigate the effects of extracts of diesel exhaust particles (DEP) on Th1 and Th2 immune responses. In order to separate compounds from DEP different in hydrophobicity, a single DEP sample was consecutively extracted with hexane (HEX-DEP), benzene (BEN-DEP), dichloromethane (DIC-DEP), methanol (MET-DEP), and 1M ammonia (AMM-DEP). The last unextracted residue (UNE-DEP) was also used to test its effect on immune responses. To immunize mice, hen egg lysozyme (HEL) was injected i.p. (day 0). Varying doses of DEP, each DEP extract, and UNE-DEP were intranasally administered every 2 days from days 0 to 18. Anti-HEL IgG2a antibodies in sera and IFN-γ secreted from spleen cells were measured as an indicator of Th1 immune responses, while anti-HEL IgG1 antibodies and IL-4 as that of Th2 responses. The results showed that treatment with DEP and DIC-DEP increased both Th1 and Th2 responses to HEL. UNE-DEP facilitated Th1 but not Th2 responses, while MET- and AMM-DEP administration was followed by enhancement of Th2 but not Th1 responses. Neither HEX- nor BEN-DEP modulated Th1 as well as Th2 responses. These results suggest that DEP contain various compounds different in hydrophobicity which may affect both Th1 and Th2, Th1 but not Th2, and Th2 but not Th1 immune responses.
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PMID:Effects of diesel exhaust particle extracts on Th1 and Th2 immune responses in mice. 1259 83

In both humans and animals, immunoglobulin (Ig)G autoantibodies are less frequent but more pathogenic than IgM autoantibodies, suggesting that controls over Ig isotype switching are required to reinforce B cell self-tolerance. We have used gene targeting to produce mice in which hen egg lysozyme (HEL)-specific B cells can switch to all Ig isotypes (SWHEL mice). When crossed with soluble HEL transgenic (Tg) mice, self-reactive SWHEL B cells became anergic. However, in contrast to anergic B cells from the original nonswitching anti-HEL x soluble HEL double Tg model, self-reactive SWHEL B cells also displayed an immature phenotype, reduced lifespan, and exclusion from the splenic follicle. These differences were not related to their ability to Ig class switch, but instead to competition with non-HEL-binding B cells generated by VH gene replacement in SWHEL mice. When activated in vitro with B cell receptor (BCR)-independent stimuli such as anti-CD40 monoclonal antibody plus interleukin 4 or lipopolysaccharide (LPS), anergic SWHEL double Tg B cells proliferated and produced IgG anti-HEL antibodies as efficiently as naive HEL-binding B cells from SWHEL Ig Tg mice. These results demonstrate that no intrinsic constraints to isotype switching exist in anergic self-reactive B cells. Instead, production of IgG autoantibodies is prevented by separate controls that reduce the likelihood of anergic B cells encountering BCR-independent stimuli. That bacteria-derived LPS could circumvent these controls may explain the well-known association between autoantibody-mediated diseases and episodes of systemic infection.
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PMID:B cell receptor-independent stimuli trigger immunoglobulin (Ig) class switch recombination and production of IgG autoantibodies by anergic self-reactive B cells. 1266 43

1. We investigated the effect of bisphenol A (BPA), which binds estrogen receptors, on immune responses including production of antigen-specific antibodies, proliferative responses of lymphoid cells, and Th1 and Th2 responses. 2. For this investigation, mice were p.o. given varying doses including 3, 30, 300, and 3000 micro g kg(-1) of BPA immediately after immunization with hen egg lysozyme (HEL) (day 0) and then daily by day 20. On day 21, anti-HEL IgG antibodies in sera and proliferative responses of spleen cells to the antigen were measured. Anti-HEL IgG2a antibodies and IFN-gamma secreted from splenic lymphocytes were also measured as indicators of Th1 immune responses, while anti-HEL IgG1 antibodies and IL-4, as those of Th2 responses. 3. The results showed that treatment with 3000 micro g kg(-1) of BPA was followed by a significant increase in anti-HEL IgG as well as the antigen-specific cell proliferation. Anti-HEL IgG2a production and IFN-gamma secretion were significantly enhanced in mice treated with 300 and 30 micro g kg(-1) of BPA, respectively, while anti-HEL IgG1 production and IL-4 secretion were augmented in animals given 3000 and 300 micro g kg(-1) of the chemical, respectively. 4. Augmentation of these immune responses was also observed in mice exposed to 0.3-30 micro g kg(-1) of estradiol, although Th1 responses appeared to be more sensitive to the sex hormone than Th2 responses. 5. These results suggest that BPA may play a role in augmenting immune responses, especially Th1 responses.
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PMID:Effects of bisphenol A on antigen-specific antibody production, proliferative responses of lymphoid cells, and TH1 and TH2 immune responses in mice. 1271 27

In pigs, protection against the toxigenic extra-cellular bacterium Actinobacillus pleuropneumoniae was correlated with an increased IgG(1):IgG(2) ratio of haemolytic toxin-specific antibodies. In all species so far studied, IgG isotype expression is controlled by Type 1 (IFN-gamma, IL-12) and Type 2 (IL-4, IL-10) cytokines which dictate immune response polarization to cell-mediated (CMI) or antibody-mediated immunity (AMI), respectively. Thus, immunoglobulin (Ig) isotypes reflect Type 1 or Type 2 immune responses. Immunoglobulin isotype production by porcine B-cells cultured in the presence of recombinant porcine (rp) cytokines varies by individual, however pigs tend to generate a high IgG(1):IgG(2) ratio in response to rp IL-10 and the inverse in response to rp IFN-gamma or rp IL-12. Differential Ig isotype production should favor an isotype with a functional advantage to control the inciting infection and disease. However, functions of porcine Ig isotypes have not been described. To compare function of porcine IgM, IgG(1) and IgG(2) of defined specificity for hen eggwhite lysozyme (HEWL), Ig isotypes were affinity purified from serum by HEWL specificity and by isotype-specific mouse monoclonal antibodies. Their ability to activate complement (C') and to opsonize was tested in vitro. Porcine IgG(2) had greater guinea pig C' activating ability than did IgG(1). Neither isotype opsonized HEWL-conjugated sheep erythrocytes in vitro. Amino acid sequence analysis of IgG isotypes revealed that all subclasses have putative C' binding sites but that IgG(2a), IgG(2b) and IgG(4) were more flexible in the middle hinge region than IgG(1) and IgG(3) and would likely activate C' more efficiently. Thus, porcine IgG isotypes associated with resistance and susceptibility to disease also differ in their actual and predicted biological functions.
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PMID:Porcine Ig isotypes: function and molecular characteristics. 1279 35

Recurrent autoimmune destruction of the insulin-producing beta cells is a key factor limiting successful islet graft transplantation in type I diabetic patients. In this study, we investigated the feasibility of using an Ag-specific plasmid DNA (pDNA)-based strategy to protect pro-islets that had developed from a neonatal pancreas implanted under the kidney capsule of nonobese diabetic (NOD) mice. NOD recipient mice immunized with pDNA encoding a glutamic acid decarboxylase 65 (GAD65)-IgFc fusion protein (JwGAD65), IL-4 (JwIL4), and IL-10 (pIL10) exhibited an increased number of intact pro-islets expressing high levels of insulin 15 wk posttransplant, relative to NOD recipient mice immunized with pDNA encoding a hen egg lysozyme (HEL)-IgFc fusion protein (JwHEL)+JwIL4 and pIL10 or left untreated. Notably, the majority of grafted pro-islets detected in JwGAD65+JwIL4- plus pIL10-treated recipients was free of insulitis. In addition, administration of JwGAD65+JwIL4+pIL10 provided optimal protection for engrafted islets compared with recipient NOD mice treated with JwGAD65+JwIL4 or JwGAD65+pIL10, despite effective protection of endogenous islets mediated by the respective pDNA treatments. Efficient protection of pro-islet grafts correlated with a marked reduction in GAD65-specific IFN-gamma reactivity and an increase in IL-10-secreting T cells. These results demonstrate that pDNA vaccination can be an effective strategy to mediate long-term protection of pro-islet grafts in an Ag-specific manner and that conditions are more stringent to suppress autoimmune destruction of grafted vs endogenous islets.
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PMID:More stringent conditions of plasmid DNA vaccination are required to protect grafted versus endogenous islets in nonobese diabetic mice. 1281 32

DNA-based immunizations have been used to determine the patterns of type 1 and type 2 cytokines that can be induced in vivo for Ag-specific CD4(+) and CD8(+) T cells. IL-4 was used as a signature cytokine for a type 2 T cell response and IFN-gamma as the signature cytokine for a type 1 response. Gene gun deliveries of secreted Ags were used to bias responses toward type 2 and saline injections of cell-associated Ags to bias responses toward type 1. The studies revealed that gene gun bombardments of DNAs expressing secreted Ags strongly biased responses toward type 2, inducing IL-4-producing CD8(+) as well as CD4(+) T cells. Saline injections of DNAs expressing cell-associated Ags strongly biased responses toward type 1, inducing IFN-gamma-producing CD8(+) and CD4(+) cells. A mixed type 1/type 2 response of IFN-gamma-producing CD8(+) T cells and IL-4-producing CD4(+) T cells was found for gene gun deliveries of cell-associated Ags. Saline injections of secreted Ags raised a weakly type 1-biased response characterized by only slightly higher frequencies of IFN-gamma- than IL-4-producing CD4(+) and CD8(+) T cells. Studies in B cell knockout and hen egg lysozyme Ig transgenic mice revealed that B cells were required for the generation of IL-4-producing CD8(+) T cells.
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PMID:DNA vaccines, combining form of antigen and method of delivery to raise a spectrum of IFN-gamma and IL-4-producing CD4+ and CD8+ T cells. 1290 4

Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with approximately 32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.
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PMID:T cell proliferative responses to malondialdehyde-acetaldehyde haptenated protein are scavenger receptor mediated. 1294 35

We describe a novel antigen recognized by mAb 2E3 selectively expressed in the periphery by a subset of porcine CD4+ T cells. Both, CD4+CD8alpha- and CD4+CD8alphalow T cell subpopulations express this antigen. CD4+2E3+ T cells show phenotypical and functional characteristics of nai;ve cells. The majority of them are CD29low, CD45RAhigh, CD49dlow, CD11alow, CD18low, and SLA-II-. After mitogen activation CD4+2E3+ T cells express high levels of IL-2 mRNA, but only traces of IFN-gamma or IL-4 mRNA. Indeed a minor percentage of cells stained positive for IFN-gamma when assessed by flow cytometry. Moreover, CD4+2E3+ T cells did not proliferate in response to the recall antigen lysozyme, although they did efficiently to the mitogen ConA. By contrast, CD4+2E3- T cells show phenotypical and functional characteristics of primed cells. They express markers associated to a memory phenotype, respond to the recall antigen lysozyme, and produce high amounts of IFN-gamma and IL-4.
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PMID:2E3, a new marker that selectively identifies porcine CD4+ naive T cells. 1464 90

To examine the effects of cytokine environment at the time of antigenic exposure on T-cell cytokine profiles following T-cell-antigen presenting cell (APC) interaction, pig monocyte-derived dendritic cells (mDCs) were treated with hen egg white lysozyme (HEWL) or killed Mycobacterium tuberculosis (Mtb) alone or with a recombinant pig cytokine (TNF-alpha, interleukin (IL)-12, IL-10, interferon (IFN)-gamma or IL-6) and then incubated with autologous T-cell-enriched lymphocytes. Messenger RNA was isolated from the T-cells and used to evaluate the effects of treatment on IL-12p35, IFN-gamma, IL-4, IL-10 and IL-13 expression using RT-PCR. T-cells exposed to HEWL-treated mDCs expressed high IL-13 and moderate IL-10 and IFN-gamma, suggesting T-helper 2 (Th-2) bias. Addition of any cytokine during HEWL treatment of mDCs reduced subsequent expression of IL-10 and IL-13 by T-cells. Added IL-12 increased IFN-gamma mRNA. T-cells exposed to Mtb-treated mDCs expressed increased IFN-gamma and decreased IL-10 suggesting Th-1 bias. Addition of cytokines to mDCs treated with Mtb altered T-cell cytokine mRNA expression such that TNF-alpha, IFN-gamma or IL-12 increased IFN-gamma; IL-12 and IFN-gamma suppressed IL-10, while IL-10 and IL-12 enhanced IL-13. Messenger RNA for IL-4 and IL-12p35 was not detected in the T-cells. Results suggest Th-1/Th-2 type response bias in pigs T-cells as a function of antigen type and that cytokine environment at the time of antigen-mDC interaction alters cytokine profiles of T-cells responding to antigen-pulsed mDCs. Hence, cytokines may allow designed steering of porcine immune response.
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PMID:Th-1/Th-2 type cytokine profiles of pig T-cells cultured with antigen-treated monocyte-derived dendritic cells. 1516 Oct 79

Immunologic examinations were performed in 111 patients with uveitis concurrent with a variety of systemic pathologies, including 85 males and 26 females, mean age--32.4 +/- 5.8. A higher IL-6 content in blood serum (BS) and in lachrymal fluid (LF) was detected in all patients. The IL-4 content was lower in uveitis associated with ankylosing spondylitis and with Reuter's disease, whereas, it was higher in juvenile rheumatoid arthritis. The systemic immunity changes were related with the hemostasis impairments in the phagocytic, humoral and cellular chains: an enhanced functional activity of phagocyte cells, a lower absolute quantity of T-lymphocytes, a higher count of B-cells, a reduced concentration of IgM and of circulating immune complexes (CIC), and a diminished general hemolytic activity of the complement in BS. A reduced concentration of the secretory fraction of IgA, IgG and IgM concurrent with higher concentrations of IgA, C3- and C4 complement components, CIC and of lysozyme activity in LF was detected in the local immunity system.
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PMID:[Immunologic peculiarities of uveitis concurrent with systemic pathologies]. 1538 43


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