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)

This study was undertaken to determine whether cyclooxygenase (COX)-2, the critical enzyme in the production of febrigenic prostaglandin (PG) E(2), may be involved centrally in the fever induced in mice by homologous interleukin (IL)-6, macrophage inflammatory protein (MIP)-1 beta, and interleukin (IL)-18, a member of the pyrogenic IL-1 beta family. To this end, the core temperatures (Tc) of COX-1 and COX-2 gene-ablated mice and of their normal wild-type (WT) counterparts were recorded after intracerebroventricular (i.c.v.) challenge with recombinant murine (rm) IL-6 (10 ng/mouse), rmMIP-1 beta (20 pg/mouse), rmIL-18 (0.01-1 microgram/mouse), rmIL-1 beta (positive control; 0.1 microgram/mouse), or their vehicle (0.1% bovine serum albumin [BSA] in sterile phosphate-buffered saline [PBS]; 5 microl/mouse). rmIL-6 caused a approximately 1 degrees C T(c) rise in WT mice that peaked at approximately 120 min and gradually recovered over the next 3 h; COX-1(-/-) mice exhibited a relatively faster (peak at 45 min) and shorter (recovery at 150 min) febrile course, whereas COX-2(-/-) mice did not develop fever. rmMIP-1 beta induced a 1 degrees C fever (peak at 60 min) with a long time course (recovery incomplete at 300 min) in both WT and COX-2(-/-) mice; COX-1(-/-) mice displayed a quick-onset (peak at 40 min) and shorter (recovery at approximately 240 min) fever. rmIL-18 did not cause any thermal response at any dose whether administered intraperitoneally (i.p.) or i.c.v. in WT mice; COX gene-ablated mice, therefore, were not tested. These data indicate that COX-2-dependent PGE(2) is critical for the febrile response to IL-6, but not to MIP-1 beta. IL-18 i.p. or i.c.v. is not pyrogenic.
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PMID:Intracerebroventricular interleukin-6, macrophage inflammatory protein-1 beta and IL-18: pyrogenic and PGE(2)-mediated? 1460 75

A hallmark of renal cell carcinoma (RCC) invasion is its ability to degrade ECM by local production of gelatinase enzymes. Although many studies on RCC have demonstrated the importance of MMPs, very little information is currently known regarding the effect of inducers and inhibitors. We therefore investigated the effect of inducers and inhibitors on RCC 786-0 in vitro. Human RCC 786-0 (ATCC) was grown in RPMI medium supplemented with 10% FBS, penicillin, and streptomycin in 24-well tissue plates. At near confluence, the cells were washed with PBS; the serum-free medium was incubated with various inducers: phorbol ester (PMA), tumor necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL-1beta) and lipopolysaccharides (LPS). Cells were also incubated with inhibitors: EGCG, doxycycline, and a nutrient mixture with and without PMA; retinoic acid, dexamethasone, H-7; actinomycin D, or cyclohexamide. After 24 h, the medium was removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography. RCC 786-0 secreted two bands, a major band corresponding to MMP-2 and a faint band corresponding to MMP-9. PMA and TNF-alpha, with increased concentration, increased MMP-9 secretion, while IL-1beta and LPS did not significantly modify MMP-9 activity. MMP-2 secretion was not affected by any of the inducers. All the inhibitors tested without and with PMA showed a dose-dependent decrease in both MMP-2 and -9 expression. Further studies are in progress to confirm the role of MMP-9 on Matrigel invasion using PMA, cytokines, and LPS.
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PMID:Modulation of human renal cell carcinoma 786-0 MMP-2 and MMP-9 activity by inhibitors and inducers in vitro. 1672 Sep 25

Serum-mediated reduction in bacterial count and expression of a number of immune response genes in the blood of Atlantic cod, Gadus morhua were investigated following intraperitoneal vaccination with heat-killed Listonella (Vibrio) anguillarum. Blood was collected from the caudal vein of both vaccinated and non-vaccinated (PBS-injected) fish at 0, 1, 3, 7 and 10 days post-vaccination (dpv). Serum protein concentration and antibacterial activity of the serum samples were determined. Whole blood was used for semi-quantitative RT-PCR of immune-related genes. Total serum protein was not significantly different between the vaccinated and non-vaccinated groups. Sera from the vaccinated fish significantly reduced L. anguillarum count on 3 dpv, with reductions of at least 2 log colony forming units per ml (CFU/ml) relative to the non-vaccinated fish. Expression of antibacterial genes, bactericidal/permeability-increasing protein/lipopolysaccharide-binding protein (BPI/LBP), g-type lysozyme and transferrin was significantly upregulated in the vaccinated fish, with maximum expression within 7 dpv. Cytotoxic-related and cell-mediated immunity genes such as, apolipoprotein A-I and the non-specific cytotoxic cell receptor protein (NCCRP-1) had maximum expression at 3 and 7 dpv, respectively. Significant upregulation in expression of pro-inflammatory cytokines, IL-1 beta and IL-8 was also observed in the vaccinated fish at 1 dpv. The upregulation of immune response genes following vaccination provides valuable information in the understanding of immune mechanisms against vibriosis in Atlantic cod particularly on the acute phase response during bacterial infection.
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PMID:Intraperitoneal vaccination of Atlantic cod, Gadus morhua with heat-killed Listonella anguillarum enhances serum antibacterial activity and expression of immune response genes. 1822 48

Galectin-9 up-regulated Fc gamma RIIb expression of mouse peritoneal macrophages in vitro but down-regulated Fc gamma RIII expression. Galectin-9-treated macrophages stimulated with immune complexes (IC) produced less TNFalpha and IL-1 beta but more IL-10 than PBS-treated macrophages. Macrophage enhancing effects on IC-induced C5a and neutrophil chemotactic activity were also diminished for galectin-9-treated macrophages. In galectin-9-treated mice, the severity of IC-induced arthritis was reduced, as were pro-inflammatory cytokine levels in inflamed joints and serum C5a. Fc gamma RIIb expression of macrophages from galectin-9-treated mice was up-regulated, whereas Fc gamma RIII expression was down-regulated. Macrophages from galectin-9-treated mice produced less TNFalpha and IL-1 beta but more IL-10 than PBS-treated mice. Disease severity of galectin-9-transgenic mice was milder than wild-type mice, whereas that of galectin-9-deficient mice was exaggerated. Furthermore, macrophage Fc gamma RIIb expression in galectin-9-deficient mice was down-regulated, while Fc gamma RIII expression was up-regulated. These results suggest that galectin-9 suppresses IC-induced inflammation partly by regulating Fc gamma R expression on macrophages.
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PMID:Galectin-9 ameliorates immune complex-induced arthritis by regulating Fc gamma R expression on macrophages. 1980 Aug 50

The mitogen-activated protein (MAP) kinase phosphatase (MKP) family plays an important function in regulating the pro-inflammatory cytokines by deactivating MAP kinases. MKP-1 is essential for the dephosphorylation of p38 MAP kinase that regulates expression of IL-6, TNF-alpha, and IL-1 beta. We hypothesized that MKP-1 regulates inflammatory bone loss in experimental periodontitis. Wild-type and Mkp-1(-/-) mice received A. actinomycetemcomitans LPS injection in the palatal region or PBS control 3 times/wk for 30 days. Mice were killed, and maxillae were assessed by microcomputed tomography, histological analysis, and TRAP staining for measurement of bone loss, extent of inflammation, and degree of osteoclastogenesis. Results indicated that, in LPS-injected Mkp-1(-/-) mice, significantly greater bone loss occurred with more inflammatory infiltrate and a significant increase in osteoclastogenesis compared with Mkp-1(-/-) control sites or either wild-type group. Analysis of these data indicates that MKP-1 plays a key role in the regulation of inflammatory bone loss.
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PMID:MAP kinase phosphatase-1 protects against inflammatory bone loss. 1986 41

Patients bitten by Loxosceles spiders generally manifest marked local inflammatory reaction and dermonecrosis. This report evaluated edema formation, leukocyte infiltration and release of inflammatory mediators at the injection site of Loxosceles gaucho venom. BALB/c mice were i.d. injected with venom and thereafter paws were disrupted and homogenized to obtain differential counts of migrated cells, as well to assay the levels of cytokines, chemokines and lipid mediators. Increased footpad thickness was detected as soon as 30 min after venom injection, and 24h later was similar to that of the control group. Loxosceles venom mildly augmented the recruitment of leukocytes to the footpad in comparison with PBS-injected mice. Moreover, it stimulated the release of IL-6, MCP-1 and KC at 2 and 24h after venom injection. In addition, higher levels of PGE(2) were detected 30 min after venom injection in comparison with control group. However, the venom failed to increase levels of IL-1 beta, TNF-alpha, TXB(2) and LTB(4). Our results demonstrate that L. gaucho venom evokes an early complex inflammatory reaction, stimulating the secretion of pro-inflammatory cytokines and lipid mediators (PGE(2)), and recruiting leukocytes to the footpad which contribute to the local reaction induced by L. gaucho venom.
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PMID:Inflammatory mediators generated at the site of inoculation of Loxosceles gaucho spider venom. 2061 25


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