Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that tumor necrosis factor-alpha (TNF-alpha) would be teratogenic in mice due in part to its effects on zinc metabolism. In Experiment 1, nonpregnant mice were injected with a single dose of TNF-alpha (40,000 U) or PBS and then received a 65Zn-labeled meal. Mice killed 10 h after TNF-alpha treatment had high liver 65Zn and low plasma 65Zn, compared with controls. In Experiment 2, gestation day 8 (GD 8) mice were injected with PBS or TNF-alpha and then received a 65Zn-labeled meal. Dams killed 10 h after TNF-alpha treatment had higher liver and kidney 65Zn and lower plasma and embryonic 65Zn accumulation than controls. In Experiment 3, TNF-alpha dosing from GD 7-12 was associated with high maternal liver Zn and metallothionein concentrations on GD 13 and a high frequency of exencephaly on GD 18. In Experiment 4, dams fed diets containing 4.5, 12.5 or 50.0 micrograms Zn/g were given PBS or TNF-alpha on GD 7-12. Gross fetal defects were not observed in the PBS-treated litters evaluated on GD 18. In contrast, TNF-alpha-treated litters were characterized by multiple defects, with the incidence and severity being highest in the low Zn diet group. In Experiment 5, embryos cultured in serum from TNF-alpha-treated animals exhibited a high frequency of defects; the developmental toxicity of this serum was ameliorated when it was supplemented with Zn. Thus, the developmental toxicity of TNF-alpha is due in part to its influence on Zn metabolism.
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PMID:Tumor necrosis factor-alpha alters maternal and embryonic zinc metabolism and is developmentally toxic in mice. 772 94

Recently an alveolar macrophage (AM)-depleted rat model has been characterized and it has been demonstrated that AM are required for the endotoxin-induced tumor necrosis factor (TNF) release into the alveolar space (J Appl Physiol 1993;74:2812-2819). The current study investigated the response of AM-depleted rats to hyperoxia and evaluated the potential role of AM in the pathogenesis of pulmonary O2 toxicity. Rats were insufflated with Hanks' balanced salt solution (HBSS), liposome-encapsulated phosphate-buffered saline (PBS-liposomes), or liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposomes) and 2 days later exposed to 100% O2. The effect of hyperoxia was assessed by parameters of O2-induced lung injury (e.g., hematocrit value, pleural effusion volume, effusion protein to plasma protein ratio, and alveolar lavage fluid protein content), TNF release into the alveolar space, and survival. Insufflation of Cl2MDP-liposomes, but not HBSS or PBS-liposomes, caused a sustained depletion of > 70% AM, which was associated with a slight but significant increase in the number of lavageable neutrophils. Twenty percent of AM-depleted rats survived longer than 74 h of O2 exposure, while all rats insufflated with HBSS or PBS-liposomes died within 74 h (p < .05). No significant differences were detected in alveolar TNF release or in the extent of O2-induced lung injury.
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PMID:Response of alveolar macrophage-depleted rats to hyperoxia. 772 76

Polysaccharides (EP) isolated from large scale plant cell cultures of Echinacea purpurea, have been shown to activate human and murine phagocytes. In this study we investigated the influence of EP on the nonspecific immunity in immunodeficient mice. EP was effective in activating peritoneal macrophages isolated from animals after administration of cyclophosphamide (CP) or cyclosporin A (CsA). EP-treated macrophages exhibited increased production of tumor necrosis factor-alpha (TNF) and enhanced cytotoxicity against tumor target WEHI 164 as well as against the intracellular parasite Leishmania enrietti. After a CP-mediated reduction of leukocytes in the peripheral blood, the polysaccharides induced an earlier influx of neutrophil granulocytes as compared to PBS-treated controls. EP treatment of mice, immunosuppressed with CP or CsA, restored their resistance against lethal infections with the predominantly macrophage-dependent pathogen Listeria monocytogenes and predominantly granulocyte-dependent Candida albicans. Further, the effects of EP in allogeneic bone marrow chimeric mice are discussed. These findings may have therapeutical implications in prophylactic treatment of opportunistic infections.
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PMID:Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenes. 837 43

Inflammatory cytokines play a key role in the myocardial injury produced by viral myocarditis. Although interleukin-6 (IL-6) reportedly possesses antiviral properties, its effect in viral myocarditis is unclear. To investigate the role of IL-6 in viral myocarditis induced by encephalomyocarditis virus (EMCV) in mice, we evaluated (1) the survival rate following IL-6 administration, (2) the viral titer in the heart, (3) viral replication in the heart by in situ hybridization, (4) histopathological changes using immunohistochemical staining, (5) neutralizing antibody against EMCV, (6) circulating interferon and tumor necrosis factor-alpha (TNF-alpha), (7) viral suppression in vitro by IL-6, and (8) natural killer (NK)-cell activity. Eight-week-old C3H/HeJ mice were injected intraperitoneally with EMCV (day 0) and were also injected subcutaneously twice daily for 4 consecutive days with 10 micrograms/0.1 mL of human IL-6 on day -4 (group A), day 0 (group B), or day +4 (group D) for 4 days. As a control, 0.1 mL PBS instead of IL-6 was injected on day 0 for 4 days (group C). Certain mice were killed on day 4. The myocardial virus titers, viral replication in situ, and NK-cell activity in the spleen were determined. Decreased viral titer and viral replication in the heart reduced the titer of circulating TNF-alpha, and lower NK-cell activity was observed in group B versus group C (control group). The titer of neutralizing antibodies against EMCV was significantly (P < .05) increased in group B compared with group C. The remaining mice were killed on days 10 and 30 after infection. The ratio of heart weight (HW) to body weight (BW) and myocardial injury in group B were reduced versus group C on days 10 and 30. The HW of group B on day 30 did not differ from the normal control group. The ratio of splenic weight to BW and the ratio of thymic weight to BW of group B increased on day 10, with expanded follicles observed in the spleen and enlargement of the medulla observed in the thymus. Immunohistochemical study revealed an increased percentage of macrophages in the heart and spleen of group B. In summary, IL-6 reduces myocardial damage in mice with viral myocarditis. Modification of immune responses together with reduction in viral replication appears to be the mechanism of the IL-6 effect. Although IL-6 is likely important in the process of viral antigen presentation, early activation of immune responses and attenuation of viral replication appear most significant, as reflected in the limited time window during which IL-6 is effective in myocarditis.
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PMID:Modification of viral myocarditis in mice by interleukin-6. 862 Jun 5

It has been reported that tumor necrosis factor-alpha (TNF-alpha) derived from luteal macrophage is concerned with luteolysis. In the present study, to evaluate the correlation between TNF-alpha and regression of luteal blood vessels, recombinant human TNF-alpha (rh-TNF) was injected into the parenchyma of pseudopregnant rabbit ovaries. These injections were performed on day 7 of pseudopregnancy (functional luteal phase). Only Mg++ and Ca++ free phosphate buffer saline (PBS-) as the solvent was injected in the control group. Estimations of conditions in the luteal vessels after the injections was performed by observations of luteal vascular corrosion casts under a scanning electron microscope. Concentrations of serum progesterone before or after the injection were also assayed. In the control group, no change in the structure of luteal vessels was observed after PBS-injection, but regressing blood vessels with strictures, obstructions and rugged surfaces on the vessels were observed, and also concentrations of serum progesterone decreased noticeably after rh-TNF injection. These findings suggest that TNF-alpha plays a role in angiolysis through luteolysis in the rabbit corpus luteum.
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PMID:Effects of TNF-alpha injection into the ovarian parenchyma on luteal blood vessels in rabbits. 882 17

Curcumin is a naturally occurring, dietary polyphenolic phytochemical that is under preclinical trial evaluation for cancer preventive drug development and whose working pharmacological actions include anti-inflammation. With respect to inflammation, in vitro, it inhibits the activation of free radical-activated transcription factors, such as nuclear factor kappaB (NFkappaB) and AP-1, and reduces the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), and interleukin-8. Inducible nitric oxide synthase (iNOS) is an inflammation-induced enzyme that catalyzes the production of nitric oxide (NO), a molecule that may lead to carcinogenesis. Here, we report that in ex vivo cultured BALB/c mouse peritoneal macrophages, 1-20 microM of curcumin reduced the production of iNOS mRNA in a concentration-dependent manner. Furthermore, we demonstrated that, in vivo, two oral treatments of 0.5 mL of a 10-microM solution of curcumin (92 ng/g of body weight) reduced iNOS mRNA expression in the livers of lipopolysaccharide(LPS)-injected mice by 50-70%. Although many hold that curcumin needs to be given at dosages that are unattainable through diet to produce an in vivo effect, we were able to obtain potency at nanomoles per gram of body weight. This efficacy is associated with two modifications in our preparation and feeding regimen: 1) an aqueous solution of curcumin was prepared by initially dissolving the compound in 0.5 N NaOH and then immediately diluting it in PBS; and 2) mice were fed curcumin at dusk after fasting. Inhibition was not observed in mice that were fed ad lib., suggesting that food intake may interfere with the absorption of curcumin.
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PMID:In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. 971 15

Interleukin 2 (IL-2) expressing plasmid and interleukin 6 (IL-6)-expressing plasmid were encapsulated in liposome and administrated intratumoraly into tumor-bearing mice 4 days after subcutaneous inoculation of B16F10 melanoma cells. The results showed that treatment of tumor-bearing mice with IL-2 gene or IL-6 gene transfer inhibited the growth of subcutaneous tumor and prolonged the survival of tumor-bearing mice significantly when compared with the treatment of PBS or control gene transfer mediated by liposome (P < 0.01). Combined transfer of IL-2 gene and IL-6 gene was found to elicit inhibitory effects on the growth of B16F10 tumor more significantly and prolonged the survival period of tumor-bearing mice more obviously. We investigated the local immunity in tumor microenvironment and found that IL-2 and IL-6 gene transfer could significantly increase the expression of lymphocyte function-associated antigen-1 on tumor infiltrating lymphocytes (TIL) and MHC-I molecule on tumor cells freshly isolated from the tumor mass. The NK and CTL activity of TIL increased markedly after the combined transfer of these two cytokine genes. We also observed the systemic antitumor immune response in the tumor-bearing mice and demonstrated that NK and CTL activity of splenocytes and the production of IL-2, tumor necrosis factor and interferon-gamma from splenocytes increased obviously in mice after the combined transfer of IL-2 and IL-6 gene. In conclusion, local and systemic antitumor immunity of the tumor-bearing host could be induced efficiently after the combined gene transfer. The enhanced specific and non-specific antitumor immunity might be responsible for the more potent antitumor effects of the combined gene therapy.
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PMID:Efficient inducation of local and systemic antitumor immune response by liposome-mediated intratumoral co-transfer of interleukin-2 gene and interleukin-6 gene. 1046 6

The intraperitoneal (i.p.) treatment with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) is one of the possible therapies for tumors that are confined to the abdominal cavity. Clinical trials aiming at the exploitation of the antitumor effects of rhTNF-alpha have been largely disappointing. In this model the activity of some rhTNF-alpha derivatives was studied. Ehrlich's ascites tumor (EAT) bearing Swiss albino male mice were treated i.p. three times a week with 10 micrograms/mice of rhTNF-alpha, mutein V or mutein VI for two weeks, starting on the 4th day after tumor inoculation. Control mice received PBS. The effect of the rhTNF-alpha derivatives on the course of EAT was evaluated basing on: total ascites volume (TAV); packed cell volume (PCV); total packed cell volume (TPCV); inhibitory growth rate (IGR); cellular population of EAT fluid; morphological EAT cell changes and mean survival time (MST). In the study mutein VI had only a slight effect on MST but significant on TAV- and TPCV-IGR (p < 0.001). In mice treated with rhTNF-alpha and mutein V the enhancement of MST (p < 0.01) was accompanied by TAV- and TPCV-IGR (p < 0.001). The number of EAT cells in ascites decreased after rhTNF-alpha and mutein V administration (p < 0.001). We conclude that treatment with high-dose of this modified molecule lacking the possibility of binding with p75R and not producing so intensified side effects is likely to find wider application in therapy and prevent the ascites growth just as rhTNF-alpha dosage.
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PMID:The antitumor effect of intraperitoneal treatment with rhTNF-alpha muteins on Ehrlich ascites tumor growth. 1074 Jun 51

In mice, individual dietary omega-3 polyunsaturated fatty acids n-3 (PUFA) were found to be sufficient to effect the changes in circulating interleukin (IL)-12 and interferon (IFN)-gamma levels that were previously seen in fish oil-fed mice. Weanling female C3H mice were fed one of five experimental diets. All five diets met all known nutritional requirements for mice and differed only in the fat source. After 4 weeks, mice were challenged with live Listeria monocytogenes or sterile PBS. Twenty-four hours after infection, n-3 PUFA-fed mice had significantly lower circulating IL-12 p70 and IFN-gamma than mice fed the control diet (P<.01). In addition, splenic cytokine mRNA for IL-12 p40, tumor necrosis factor-alpha, and IL-1beta were lower in infected mice fed n-3 PUFA-containing diets than in mice fed the olive oil ethyl esters control diet. The reduction of IL-12 and IFN-gamma production by n-3 PUFA may have important implications for host infectious disease resistance.
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PMID:Consumption of eicosapentaenoic acid and docosahexaenoic acid impair murine interleukin-12 and interferon-gamma production in vivo. 1094 84

We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fever in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF-alpha) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858-R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D-galactosamine (D-gal) was used to selectively inhibit liver protein synthesis. D-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 microg/kg ip) was injected 24 h post-heat exposure. Treatment with D-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D-gal and subsequently with LPS demonstrated a profound fall in core temperature 10--18 h post-LPS. A significant increase of serum TNF-alpha accompanied this effect of D-gal on fever. Heat-conditioned animals receiving D-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS.
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PMID:Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats. 1120 60


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