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)

Hyperlipidemia promotes oxidant stress, inflammation, and atherogenesis in apolipoprotein E-deficient (ApoE((-/-))) mice. Mice transgenic for lysozyme (LZ-Tg) are resistant to acute and chronic oxidative stress and have decreased circulating levels of pro-oxidant advanced glycation end-products (AGEs). Herein we report that TIB-186 macrophages transduced with adenovirus-expressing human LZ (AdV-LZ) containing the AGE-binding domain facilitated AGE uptake and degradation and that AdV-LZ-transduced macrophages and peritoneal macrophages from LZ-Tg mice suppressed the AGE-triggered tumor necrosis factor-alpha response. We assessed atherosclerosis in LZ-Tg mice crossed with ApoE((-/-)) mice (LZ/ApoE((-/-))) and found increased serum LZ levels and decreased AGE and 8-isoprostanes levels, although hyperlipidemia remained similar to ApoE((-/-)) controls. Atherosclerotic plaques and neointimal lesions at the aortic root and descending aorta were markedly decreased (by 40% and 80%, respectively) in LZ/ApoE((-/-)) versus ApoE((-/-)) mice, as were inflammatory infiltrates. The arterial lesions following femoral artery injury in LZ/ApoE((-/-)) mice were suppressed (intimal to media ratio decreased by 50%), as were AGE deposits and vascular smooth muscle cell activation, compared to ApoE((-/-)) mice. Despite hyperlipidemia, development of atheroma and occlusive, inflammatory arterial neointimal lesions in response to injury was suppressed in LZ/ApoE((-/-)) mice. This effect may be due to the antioxidant properties of LZ, which is possibly linked to the AGE-binding domain region of the molecule.
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PMID:Reduced acute vascular injury and atherosclerosis in hyperlipidemic mice transgenic for lysozyme. 1681 82

Although fish immunology has progressed in the last few years, the contribution of the normal endogenous microbiota to the overall health status has been so far underestimated. In this context, the establishment of a normal or protective microbiota constitutes a key component to maintain good health, through competitive exclusion mechanisms, and has implications for the development and maturation of the immune system. The normal microbiota influences the innate immune system, which is of vital importance for the disease resistance of fish and is divided into physical barriers, humoral and cellular components. Innate humoral parameters include antimicrobial peptides, lysozyme, complement components, transferrin, pentraxins, lectins, antiproteases and natural antibodies, whereas nonspecific cytotoxic cells and phagocytes (monocytes/macrophages and neutrophils) constitute innate cellular immune effectors. Cytokines are an integral component of the adaptive and innate immune response, particularly IL-1 beta, interferon, tumor necrosis factor-alpha, transforming growth factor-beta and several chemokines regulate innate immunity. This review covers the innate immune mechanisms of protection against pathogens, in relation with the installation and composition of the normal endogenous microbiota in fish and its role on health. Knowledge of such interaction may offer novel and useful means designing adequate therapeutic strategies for disease prevention and treatment.
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PMID:A review on the interactions between gut microbiota and innate immunity of fish. 1808 45

Immune responses in the testis are regulated in a way that provides protection for the developing male germ cells, while permitting qualitatively normal inflammatory responses and protection against infection. In addition, germ cells are potent targets for the growth factors and cytokines which regulate the reproductive process. Our study analyzes for the first time the pattern of expression of several immune-relevant genes in the gonad of a seasonal breeding teleost fish. The immune molecules analyzed include (i) inflammatory molecules, such as interleukin-1b (il1b), il6, tumor necrosis factor-a (tnfa), cyclooxygenase-2 (cox2) and the NADPH oxidase subunit p40(phox) (ncf4 gene); (ii) the anti-inflammatory cytokine transforming growth factor-b1 (tgfb1) and its type 2 receptor tgfbr2; (iii) innate immune receptors, including toll-like receptor 9 (tlr9), tlr5, tlr22 and macrophage-colony stimulating factor receptor (mcsfr); (iv) lymphocyte receptors, such as the beta subunit of T-cell receptor (Tcrb) and the heavy chain of immunoglobulin M (ighm); (v) the anti-bacterial molecules lysozyme (lyz), hepcidin (hamp) and complement component 3 (c3); (vi) the anti-viral molecule myxovirus (influenza) resistance protein (mx); and (vii) molecules related to leukocyte infiltration, including the CC chemokine ccl4, the CXC chemokine il8 and the leukocyte adhesion molecule E-selectin (Sele). Notably, all of them show a pattern of expression that depends on the reproductive stage of the first two reproductive cycles when the fish develop and function as males. Furthermore, we demonstrate that some of these immune-relevant molecules, such as Il1b and Mcsfr, are produced by germ cells (Il1b) and ovarian and testicular somatic cells (Mcsfr). These data suggest that, as occurs in mammals, there is a critical balance between immune molecules and that these may play an essential role in the orchestration of gametogenesis and the maintenance of gonad tissue homeostasis in fish.
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PMID:Pattern of expression of immune-relevant genes in the gonad of a teleost, the gilthead seabream (Sparus aurata L.). 1832 94

The increasing economic importance of fish parasitoses for aquaculture and fisheries has enhanced the interest in the defence mechanisms against these infections. Both innate and adaptive immune responses are mounted by fish to control parasite infections, and several mechanisms described for mammalian parasitoses have also been demonstrated in teleosts. Innate immune initiation relies on the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognizing receptors (PRRs). A number of PRRs, mainly Toll-like receptors (TLRs), have been characterized in fish, and some molecules susceptible of functioning as PAMPs are known for some fish parasites. A lectin-carbohydrate interaction has also been described in some host fish-parasite systems, thus probably involving C-type lectin receptors. Inflammatory reactions involving cellular reactions, as phagocytosis and phagocyte activity (including oxidative mechanisms), as well as complement activity, are modulated by many fish parasites, including mainly ciliates, flagellates and myxozoans. Besides complement, a number of humoral immune factors (peroxidases, lysozyme, acute-phase proteins) are also implicated in the response to some parasites. Among adaptive responses, most data deal with the presence of B lymphocytes and the production of specific antibodies (Abs). Although an increasing number of T-cell markers have been described for teleosts, the specific characterization of those involved in their response is far from being obtained. Gene expression studies have demonstrated the involvement of other mediators of the innate and adaptive responses, i.e., cytokines [interleukins (IL-1, IL-8), tumor necrosis factor (TNF), interferon (IFN)], chemokines (CXC, CC), as well as several oxidative enzymes [inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX-2)]. Information is scarcer for factors more directly linked to adaptive responses, such as major histocompatibility (MH) receptors, T cell receptors (TCRs) and IgM. Expression of some immune genes varied according to the phase of infection, and proinflammatory cytokines were mainly activated in the early stages. Gene expression was generally higher in the target tissues for some skin and gill parasites, as Ichthyophthirius multifiliis, Neoparamoeba spp. and Lepeophtheirus salmonis, thus confirming the relevance of mucosal immunity in these infections. The existence of protective responses has been demonstrated for several fish parasites, both in natural infections and in immunization studies. Most information on the mechanisms involved in protection deals with the production of specific Abs. Nevertheless, their levels are not always correlated to protection, and the precise involvement of immune mechanisms in the response is unknown in many cases. No commercial vaccine is currently available for piscine parasitoses, although experimental vaccines have been assayed against I. multifiliis, Cryptobia salmositica and scuticociliates. The known information points to the need for integrated studies of the mechanisms involved in protection, in order to choose the optimum antigen candidates, adjuvants and formulations.
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PMID:Fish immunity and parasite infections: from innate immunity to immunoprophylactic prospects. 1878 35

Lactobacillus delbrueckii UFV-H2b20 has been shown to increase clearance of bacteria injected into the blood of germ-free mice. Moreover, it induces the production of type 1 cytokines by human peripheral mononuclear cells. The objective of the present study was to investigate the production of inflammatory cytokines [interleukin-12 (IL-12 p40), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma)] triggered in vitro by live, heat-killed or lysozyme-treated L. delbrueckii UFV-H2b20 and in vivo by a live preparation. Germ-free, L. delbrueckii-monoassociated and lipopolysaccharide (LPS)-resistant C3H/HeJ mice were used as experimental models. UFV-H2b20 induced the production of IL-12 p40 and TNF-alpha by peritoneal cells and IFN-gamma by spleen cells from germ-free or monoassociated Swiss/NIH mice and LPS-hyporesponsive mice (around 40 ng/mL for IL-12 p40, 200 pg/mL for TNF-alpha and 10 ng/mL for IFN-gamma). Heat treatment of L. delbrueckii did not affect the production of these cytokines. Lysozyme treatment decreased IL-12 p40 production by peritoneal cells from C3H/HeJ mice, but did not affect TNF-alpha production by these cells or IFN-gamma production by spleen cells from the same mouse strain. TNF-alpha production by peritoneal cells from Swiss/NIH L. delbrueckii-monoassociated mice was inhibited by lysozyme treatment. When testing IL-12 p40 and IFN-gamma levels in sera from germ-free or monoassociated Swiss/NIH mice systemically challenged with Escherichia coli we observed that IL-12 p40 was produced at marginally higher levels by monoassociated mice than by germ-free mice (40 vs 60 ng/mL), but IFN-gamma was produced earlier and at higher levels by monoassociated mice (monoassociated 4 and 14 ng/mL 4 and 8 h after infection, germfree 0 and 7.5 ng/mL at the same times). These results show that L. delbrueckii UFV-H2b20 stimulates the production of type 1 cytokines in vitro and in vivo, therefore suggesting that L. delbrueckii might have adjuvant properties in infection in which these cytokines play a major role.
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PMID:Lactobacillus delbrueckii UFV-H2b20 induces type 1 cytokine production by mouse cells in vitro and in vivo. 1933 Feb 64

Phloroglucinols, garcinielliptones HA-HE (1-5), and C (6) were studied in vitro for their inhibitory effects on chemical mediators released from mast cells, neutrophils, and macrophages. Compound 6 revealed significant inhibitory effect on release of lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Compounds 3, 4, and 6 showed significant inhibitory effects on superoxide anion generation in rat neutrophils stimulated with (fMLP)/(CB), while compounds 1 and 5 revealed inhibitory effects on tumor necrosis factor-alpha (TNF-alpha) formation in macrophages stimulated with lipopolysaccharide (LPS). Compounds 1 and 3-6 showed inhibitory effects on xanthine oxidase (XO) and could inhibit the DNA breakage caused by O2(-*). Treatment of NTUB1 with 2 to 60 microM compound 3 and 5 microM cisplatin and SV-HUC1 with 9 to 60 microM 3 and 5 microM cisplatin, respectively, resulted in an increase of viability of cells. These results indicated that compounds 1 and 3-6 showed anti-inflammatory effects and antioxidant activities. Compound 3 mediates through the suppression of XO activity and reduction of reactive oxygen species (ROS), and protection of subsequent cell death.
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PMID:Phloroglucinols inhibit chemical mediators and xanthine oxidase, and protect cisplatin-induced cell death by reducing reactive oxygen species in normal human urothelial and bladder cancer cells. 1975 19

The aims of the present study were to investigate the immunomodulatory effect of a Sophora subprosrate polysaccharide (SSP1) on splenic lymphocyte proliferation, production of cytokines and antioxidant capacities in dexamethasone-induced immunosuppressed mice. The results showed that SSP1 stimulated proliferation and IFN-gamma secretion of murine splenic lymphocytes at concentrations of 50, 100, 200 or 400 mg/L in vitro. SSP1 increased the levels of interleukin-6 and tumor necrosis factor-alpha in immunosuppressed mice induced by subcutaneous injection of dexamethasone at 1.25 mg/kg. Administration of SSP1 by intraperitoneal injection significantly raised spleen index, glutathione level, glutathione peroxidase activity and lysozyme activity in the immunosuppressed mice. This suggests that SSP1 may play an important role in regulating immunological functions in mice.
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PMID:Immunomodulatory effect of a Sophora subprosrate polysaccharide in mice. 1989 97

Edwardsiella tarda is an important Gram-negative bacterium that causes systemic infections in a wide range of hosts including fish. The pathogenic mechanisms in this disease are still poorly understood in fish. Indian major carp, Labeo rohita were intraperitoneally challenged with a pathogenic isolate of E. tarda to measure sequential changes in immunity level. A significant decrease in the superoxide production, myeloperoxidase, alternative complement activity, total protein levels and antiprotease activity of serum was marked in the infected fish. However, the serum lysozyme activity and haemagglutination titre were raised in the infected fish. Similarly, a significant rise in specific antibody titre was noticed on and after 10 days post-challenge. This study also elucidates the changes in the relative expression of some immune-related genes viz., interleukin 1-beta (IL-1beta), inducible nitric oxide synthase (iNOS), complement component C3, beta(2)-microglobulin, CXCa, tumor necrosis factor-alpha (TNFalpha), and C-type and G-type lysozymes during the infection. Significant up-regulation of IL-1beta, iNOS, C3, CXCa and expression of both types of lysozyme genes was noticed at 6-12 h post-challenge (h.p.c.) whereas down-regulation of beta(2)-microglobulin and TNFalpha genes was observed after 48 h p.c. The results obtained here strengthen the understanding on molecular pathogenesis of edwardsiellosis in L. rohita.
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PMID:Immune responses and expression profiles of some immune-related genes in Indian major carp, Labeo rohita to Edwardsiella tarda infection. 2004 61

In order to advance the application of antimicrobial peptides in aquaculture, transgenic zebrafish expressing the antimicrobial peptide, epinecidin-1, were developed and are reported on here. First, we cloned the zebrafish mylz2 promoter for this purpose. To characterize the activity of the mylz2 promoter, various fragments of it were analyzed using a firefly luciferase transient expression assay, in which maximum promoter activity was found with a 2.5-kb fragment. In addition, the 2.5-kb fragment also expressed considerable red fluorescent proteins in skeletal muscles of transgenic zebrafish. Second, in order to improve the translation efficiency of the Tol2 transposase, we constructed untranslated regions (UTRs) of zebrafish ba1 globin flanked by a transposase. A transient embryonic excision assay (TEEA) and in vivo fluorescent observations showed high transposition efficiency during embryonic development. After optimization of the promoter and transgene efficiencies, transgenic zebrafish with the Epi-1/DsRed plasmid (pTLR-m2.5 K-K.Epinecidin-1/DsRed vector) were developed, and expressions of Epi-1/DsRed in muscles and blood were demonstrated by immunohistochemical staining techniques. Moreover, we also found that the Epi-1/DsRed gene was efficiently and significantly expressed in vivo against Vibrio vulnificus and Streptococcus agalactiae after injecting the bacteria and determining bacterial counts. A gene expression study using real-time RT-PCR revealed that Epi-1/DsRed itself induced endogenous MyD88 expression in vivo. After Epi-1/DsRed transgenic zebrafish were infected with V. vulnificus 204, interleukin (IL)-10, IL-22, IL-26, lysozyme, toll-like receptor (TLR)1, TLR3, TLR4a, MyD88, and nuclear factor (NF)-kappaB activating protein-like were upregulated, but IL-1beta and tumor necrosis factor-alpha were downregulated at 12h post-infection; IL-21, complement component c3b, and NF-kappaB activating protein-like were downregulated, but MyD88 was upregulated at 24h post-infection. These results suggest that using epinecidin-1 as a transgene in zebrafish can effectively inhibit bacterial growth for up to 24h after infection.
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PMID:Using an improved Tol2 transposon system to produce transgenic zebrafish with epinecidin-1 which enhanced resistance to bacterial infection. 2015 37

Hepcidin is an antimicrobial peptide (AMP) secreted by the liver during inflammation that plays a central role in mammalian iron homeostasis. But the function of hepcidin in fish is still not completely understood. We recently described three different hepcidins (named tilapia hepcidin (TH)1-5, TH2-2, and TH2-3) from tilapia Oreochromis mossambicus, the cDNA sequences were determined, the predicted peptides were synthesized, and the TH2-3 peptide showed antimicrobial activity against several bacteria. We hypothesized that TH2-3 may have a biological function like an AMP in fishes and can be used as a transgene to boost resistance against bacterial infection. To examine the antimicrobial effects of TH2-3, we produced and engineered the overexpression of TH2-3 in zebrafish (Danio rerio) and the convict cichlid (Archocentrus nigrofasciatus). The microinjected plasmid also contained a green fluorescent protein (GFP) which was used as an indicator to trace germline transmission. In vivo, transgenic TH2-3 fish (of the F3 generation) were challenged with Vibrio vulnificus (204) and Streptococcus agalactiae (SA). Results showed significant clearance of bacterial numbers of V. vulnificus (204) but not of S. agalactiae in transgenic TH2-3 fish. A gene expression study using a real-time RT-PCR revealed that transgenic TH2-3 zebrafish showed increased endogenous expressions of Myd88, tumor necrosis factor-alpha, and TRAM1 in vivo. After transgenic TH2-3 zebrafish were infected with V. vulnificus (204), interleukin (IL)-10, IL-26, lysozyme, toll-like receptor (TLR)-4a, and Myd88 were upregulated, but IL-1beta (at 12-24 h) and IL-15 (at 1-12 h) were downregulated post-infection. After transgenic TH2-3 zebrafish were infected with S. agalactiae, IL-1beta (at 1-24 h), IL-15 (at 6 h), IL-22 (at 1-6 h), and TLR3 (at 1-24 h) were downregulated, but TLR4a (at 6-12 h) and c3b (at 12 h) were upregulated post-infection. Our findings identify the TH2-3 transgene in transgenic fish as an active component of the host response to bacterial pathogens. These results suggest that using TH2-3 as a transgene in zebrafish can effectively inhibit bacterial growth, specifically the V. vulnificus (204) strain for up to 24 h.
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PMID:Tilapia hepcidin (TH)2-3 as a transgene in transgenic fish enhances resistance to Vibrio vulnificus infection and causes variations in immune-related genes after infection by different bacterial species. 2047 Aug 93


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