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1.
Tuberculosis (Edinb) ; 101S: S35-S44, 2016 12.
Article in English | MEDLINE | ID: mdl-27733245

ABSTRACT

Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli. BCG, T. cruzi, and LPS strongly induced expression of both unique and overlapping genes downstream of TLR signaling pathways including cytokines and chemokines that mediate inflammation and regulate cell death pathways. Compared to LPS, BCG failed to directly activate anti-apoptotic molecules and multiple NLR and inflammasome complex components including caspase-1, and actively repressed important signaling intermediates in AP-1 and NFκB transcription factor pathways. Both BCG and T. cruzi repressed expression of TXNIP, an anti-oxidant inhibitor that recruits caspase-1 to the NLRP3 inflammasome, while T. cruzi infection uniquely failed to activate TNF-α. These results identify unique pathogen specific strategies to activate inflammation and modulate cell death that may drive inflammatory outcomes and suggest avenues of investigation to optimize host immunity.


Subject(s)
BCG Vaccine/pharmacology , Inflammasomes/metabolism , Macrophage Activation/drug effects , Macrophages/drug effects , Macrophages/parasitology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Trypanosoma cruzi/pathogenicity , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Cell Line , Cytokines/metabolism , Host-Pathogen Interactions , Humans , Immunity, Innate/drug effects , Inflammasomes/drug effects , Inflammasomes/genetics , Inflammasomes/immunology , Lipopolysaccharides/pharmacology , Macrophages/immunology , Macrophages/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Signal Transduction/drug effects , Time Factors , Toll-Like Receptors/metabolism , Trypanosoma cruzi/immunology
2.
Phytochemistry ; 56(7): 733-9, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11314961

ABSTRACT

To investigate the bioactivities of soybean, which act on bone metabolism, we studied the effect of a soybean ethanol extract on the activity of osteoblast MC3T3-E1 cells. Soy extract (0.01-0.1 g/l) dose-dependently increased survival (P<0.05) and DNA synthesis (P<0.05) of MC3T3-E1 cells. In addition, soy extract (0.05 g/l) increased alkaline phosphatase activity (P<0.05) and collagen synthesis (P<0.05) of MC3T3-E1 cells. Moreover, the anti-estrogen tamoxifen eliminated the stimulation of MC3T3-E1 cells on the proliferation, ALP activity and collagen synthesis by soy extract, indicating that the main action of the soy extract on osteoblastic MC3T3-E1 cells is similar to that of estrogen effects. Treatment with soy extract prevented apoptosis, as assessed by a one-step sandwich immunoassay and DNA gel electrophoresis studies. This effect may be associated with the activation of the estrogen receptor, since we observed soy extract-mediated survival against apoptosis was blocked by the estrogen receptor antagonist tamoxifen in cells, further supporting a receptor-mediated mechanism of cell survival. These results suggest that osteoblast function is promoted by soy extract and that the estrogen receptor is involved in the response, thereby playing an important role in bone remodeling. In conclusion, soy extract has a direct stimulatory effect on bone formation in cultured osteoblastic cell in vitro. Presumably, dietary soy products are useful in the prevention of osteoporosis.


Subject(s)
Cell Survival/drug effects , Glycine max , Osteoblasts/drug effects , Plant Extracts/pharmacology , 3T3 Cells , Alkaline Phosphatase/metabolism , Animals , Cell Division/drug effects , Collagen/biosynthesis , DNA/biosynthesis , Ethanol , Mice , Osteoblasts/cytology , Osteoblasts/physiology , Tamoxifen/pharmacology
3.
Pest Manag Sci ; 57(12): 1155-60, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11802604

ABSTRACT

Pyribenzoxim, benzophenone O-[2,6-bis(4,6-dimethoxypyrimidin-2-yloxy)benzoyl]oxime, is a new post-emergence herbicide providing broad-spectrum weed control in rice fields. [14C]Pyribenzoxim was used to study the pharmacokinetics of the compound after oral administration of a dose of 1000 mg kg-1 to male Sprague-Dawley rats. The material balance ranged from 97.3 to 99.7% of the administered dose and urinary and fecal recovery accounted for 97.1%, with the majority of radioactivity recovered in feces (88.6%) by 168 h after treatment. Elimination as volatile products or as carbon dioxide was negligible. The following values were obtained for the compound in the blood: AUC0-168 h, 28,400 micrograms equiv hg-1; Tmax, 12 h; Cmax, 372 micrograms equiv g-1; half-life, 53 h. Radioactivity in tissue decreased from 96.1% of applied radiocarbon at 6 h to 0.4% at 168 h and the highest concentration of radioactivity among the tissues was observed in liver while the lowest residues were found in brain. The elimination half-lives of radioactivity from tissues was in the range of 7 to 77 h and Tmax values of 12, 24 and 12 h were observed for blood, liver and kidney, respectively. Except for that in the digestive tract, the tissue-to-blood ratio (TBR) was highest in the liver.


Subject(s)
Benzophenones/pharmacology , Herbicides/pharmacokinetics , Administration, Oral , Algorithms , Animals , Area Under Curve , Benzophenones/blood , Benzophenones/chemistry , Carbon Dioxide/metabolism , Carbon Radioisotopes , Chromatography, High Pressure Liquid , Feces/chemistry , Herbicides/blood , Herbicides/chemistry , Male , Molecular Structure , Rats , Rats, Sprague-Dawley , Spectrum Analysis , Tissue Distribution
4.
J Neurosci Methods ; 85(1): 63-71, 1998 Nov 01.
Article in English | MEDLINE | ID: mdl-9874142

ABSTRACT

Species-specific and species-common monoclonal antibodies (MAbs) to nerve-specific cell surface epitopes were used to compare pre-treatment techniques for nerve staining. Endogenous peroxidases were inactivated in four ways: (1) 0.3% hydrogen peroxide (H2O2); (2) 1% periodic acid (PA) (pH 1.85-1.95); (3) sodium meta-periodate (10-40 mM, pH 4.5); or (4) HCl (pH 1.80). Staining of chick and quail corneal nerves and dorsal root ganglia (DRG) nerves with the MAbs was species-specific. Staining of chick and quail corneal nerves was unaffected by pre-treatment with 0.3% H2O2, but was eliminated by pre-treatment with 1% PA. Chick and quail DRG nerve staining tolerated 0.3% H2O2, and at least one epitope also tolerated 1% PA. Corneal nerves of both chick and quail displayed concentration-dependent sensitivity to pre-treatment with sodium meta-periodate; DRG nerves were not sensitive to such pre-treatment. Corneal nerves tolerated pre-treatment with HCI (pH 1.80), whereas DRG nerves did not. These findings indicate sensitivity of corneal nerve epitopes to oxidation, in contrast with sensitivity of DRG nerve epitopes to low pH. Results also indicate that tissue trimming regulated whole-mount staining of corneal nerves, suggesting that antibodies cannot diffuse across corneal basement membranes, even after detergent extraction. However, antibodies are able to diffuse laterally into the stroma from any cut edge.


Subject(s)
Corneal Stroma/anatomy & histology , Ganglia, Spinal/anatomy & histology , Immunohistochemistry/methods , Animals , Chick Embryo , Coturnix , Epitopes/chemistry , Fluorescent Antibody Technique , Peroxidases
6.
Plant Physiol ; 112(3): 1383-1389, 1996 Nov.
Article in English | MEDLINE | ID: mdl-12226453

ABSTRACT

The mode of action of the herbicide 3,7-dichloroquinolinecar-boxylic acid (quinclorac) was examined by measuring incorporation of [14C]glucose, [14C]acetate, [3H]thymidine, and [3H]uridine into maize (Zea mays) root cell walls, fatty acids, DNA, and RNA, respectively. Among the precursors examined, 10 [mu]M quinclorac inhibited [14C]glucose incorporation into the cell wall within 3 h. Fatty acid and DNA biosynthesis were subsequently inhibited, whereas RNA biosynthesis was unaffected. In contrast to the cellulose synthesis inhibitor 2,6-dichlorobenzonitrile, quinclorac strongly inhibited cellulose and a hemicellulose fraction presumed to be glucuronoarabinoxylan. However, the synthesis of (1->3),(1->4)-[beta]-D-glucans was only slightly inhibited. The degree of inhibition was time- and dose-dependent. By 4 h after treatment, the concentration that inhibited [14C]glucose incorporation into the cell wall, cellulose, and the sensitive hemicellulose fraction by 50% was about 15, 5, and 20 [mu]M, respectively. Concomitant with an inhibition of [14C]glucose incorporation into the cell wall, quinclorac treatment led to a marked accumulation of radioactivity in the cytosol. The increased radioactivity was found mostly in glucose and fructose. However, total levels of glucose, fructose, and uridine diphosphate-glucose were not changed greatly by quinclorac. These data suggest that quinclorac acts primarily as a cell-wall biosynthesis inhibitor in a susceptible grass by a mechanism that is different from that of 2,6-dichlorobenzonitrile.

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