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Biomedical subjects

S M Ye

Publications and source records attributed to S M Ye.

7 recordsLinked to original sources
PubMed2001

Regulation of interleukin-6 gene expression in brain of aged mice by nuclear factor kappaB.

Interleukin-6 (IL-6) is increased in brain of aged mice. The purpose of this study was to determine if binding of nuclear factor kappaB (NFkappaB) to the IL-6 promoter is responsible for the age-related increase in brain IL-6. In an initial study, the effect of age on IL-6 in brain was verified as IL-6 protein was increased in brain of aged mice compared to adult and juvenile mice. Competitive RT-PCR showed that IL-6 mRNA concentration was at least 4-fold higher in aged brain compared to adult brain. Next, binding of the transcription factor NFkappaB to the IL-6 promoter in brains of 1-, 6-, and 24-month-old mice was determined. Electrophoretic mobility shift assay showed that NFkappaB activity was increased in aged brain compared to adult and juvenile brain. Moreover, glial cells cultured from aged mice showed more NFkappaB DNA-binding activity and more IL-6 mRNA and protein expression than glia from adults. However, incubating glia from aged mice in the presence of kappaB decoy inhibited these effects of age. The same was observed in vivo as intracerebroventricular injection of kappaB decoy in aged mice decreased NFkappaB activity and IL-6 mRNA and protein in brain. These results show that the DNA-binding activity of NFkappaB is increased in the brain of aged mice and that at least one consequence is increased expression of IL-6.

Age Factors↗
PubMed2001

An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice.

OBJECTIVES: The DNA-binding activity of nuclear factor kappaB (NFkappaB) is elevated in brain of aged mice, resulting in elevated levels of the inflammatory cytokine interleukin (IL)-6. The purpose of this study was to determine if in the brain of aged mice a decrease in the anti-inflammatory cytokine IL-10 contributes to the increase in IL-6. METHODS: In initial studies coronal brain sections and glial cells from adult (6-months-old) and aged (24-months-old) mice were incubated in the presence or absence of lipopolysaccharide (LPS) and the concentrations of IL-6 and IL-10 in supernatants were determined. In subsequent studies, the effect of recombinant murine IL-10 on constitutive and inducible NFkappaB activity, IL-6 mRNA expression and IL-6 protein secretion by glia cultured from brains of adult and aged mice was determined. RESULTS: Coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. This effect of age was evident in the absence and presence of LPS and suggested that a decrease in IL-10 production permitted increased IL-6 production. Consistent with this idea, treatment of glia from aged mice with recombinant IL-10 decreased both constitutive and inducible binding of NFkappaB to the IL-6 gene promoter. The decrease in NFkappaB activity was associated with a reduction of IL-6 mRNA and protein. Exogenous IL-10, however, had no effect on NFkappaB activity, which was undetectable in unstimulated glia from adult mice, and did not decrease steady-state levels of IL-6 mRNA or IL-6 protein secretion. CONCLUSIONS: Collectively, these studies suggest that IL-10 constrained IL-6 gene expression in the adult brain, but in the aged brain it decreased and thus enabled a cascade of intracellular events that increased expression of the IL-6 gene.

Aging↗
PubMed1999

Increased interleukin-6 expression by microglia from brain of aged mice.

Over expression of inflammatory cytokines in the brain may establish a state that is permissive to the onset of neurodegenerative disease. Because the occurrence of certain neurodegenerative diseases increases with age, in the present study we examined the expression of the inflammatory cytokine, interleukin-6 (IL-6), in the brain of aged mice. In an initial experiment, IL-6 was measured in crude protein extracts from brains of juvenile (1-month-old), adult (3-month-old), and aged (24-month-old) male BALB/c mice. The concentration of IL-6 in crude protein extracts from the cerebellum, cerebral cortex, and hippocampus increased with age. The increase in IL-6 was discrete, as levels in the hypothalamus were not age-dependent. To begin evaluating spontaneous IL-6 production in aging, glial cells were cultured from brains of neonate, adult, and aged mice. An age-associated increase in IL-6 mRNA and supernatant IL-6 concentration was evident, indicating glia from aged mice spontaneously express high levels of IL-6 relative to glia from adult and neonate mice. Flow cytometric analysis revealed that cultures established from aged brain compared to either adult or neonate brain comprised more microglia (i.e., MAC-1-positive cells). Furthermore, the proportion of microglia that was positive for IL-6 increased with age, whereas the proportion of astrocytes that were positive for IL-6 was not age-dependent. The present results suggest that IL-6 increases in the mouse brain with age, and that microglia cultured from aged mice spontaneously produce more IL-6 than those from neonate or adult mice. Therefore, microglia may contribute to the increased level of IL-6 present in aged brain.

Aging↗
PubMed1999

Chronic exercise increases macrophage-mediated tumor cytolysis in young and old mice.

In this study, we determined the effects of age and chronic treadmill running (16 wk; 5 days/wk; 45 min/day; 18-22 m/min) on resident peritoneal macrophage responsiveness to interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) in young (6 mo) and aged (22 mo) male BALB/cByJ mice by measuring cytolytic ability and production of reactive nitrogen products. Macrophages (>90% Mac-3(+)) were incubated with various concentrations of IFN-gamma and LPS for 24 h. After washing, P815 tumor cells were utilized as targets in a 16-h 51Cr release assay. We found that aging resulted in a significant reduction in the ability of macrophages to respond to the highest doses of IFN-gamma and LPS and kill P815 cells (46 +/- 4 vs. 34 +/- 2% in young and old mice, respectively). Exercise training significantly increased macrophage cytolysis in both age groups (66 + 7 vs. 44 + 2% in young and old mice, respectively); this effect was larger in the young mice. Macrophages from young exercised mice also produced significantly (50-60%) more NO-2; there was a tendency for higher NO-2 in old exercisers. The inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) significantly reduced macrophage cytolysis and NO-2 production and completely abrogated exercise-induced increases in these measures. RT-PCR analysis revealed significantly higher iNOS mRNA levels in macrophages obtained from the exercise-trained mice and significantly lower iNOS mRNA in old compared with young mice. We conclude that aging reduces and exercise training increases the capacity of resident peritoneal macrophages to respond to IFN-gamma and LPS with increased tumor cytolysis. Enhanced iNOS gene expression and NO-2 production are likely the contributing mechanisms of the exercise-induced enhancement of cytolysis in young mice. While L-NMMA did block the exercise-induced increase in cytolysis, exercise did not increase NO-2 or iNOS gene expression in the old mice, indicating perhaps the contribution of other cytolytic mechanisms in old mice.

Animals↗
PubMed1999

Mice deficient in interleukin-1beta converting enzyme resist anorexia induced by central lipopolysaccharide.

Interleukin-1beta (IL-1beta) is expressed in the mouse brain after intracerebroventricular injection of lipopolysaccharide (LPS) and is thought to be responsible for many of the behavioral and neuroendocrine changes that occur during inflammation. In this study we show that LPS in the brain also induces expression of interleukin-1beta converting enzyme (ICE) and that ICE is important for the characteristic anorectic response of mice to intracerebroventricular LPS. Specifically, mice that were deficient in ICE (ICE(-/-)) resisted the anorexia caused by intracerebroventricular injection of LPS but were sensitive to the anorectic properties of recombinant IL-1beta. The typical anorectic response seen in wild-type (WT) mice after LPS was restored in ICE(-/-) mice by intracerebroventricular administration of the ICE analog cathepsin G. Conversely, anorexia induced by intracerebroventricular injection of LPS in WT mice was blocked by prior intracerebroventricular injection of the ICE antagonist YVAD. CMK. Furthermore, in situ hybridization immunohistochemistry revealed intense expression of ICE mRNA in the hippocampus and dorsomedial hypothalamus of WT mice after intracerebroventricular injection of LPS. Thus ICE mRNA is expressed in brain after intracerebroventricular injection of LPS and is important for induction of anorexia, presumably because it generates mature IL-1beta. These results suggest that preventing generation of mature IL-1beta can inhibit anorexia induced by LPS in the brain and, therefore, reveal ICE as a potential target for regulating food intake during brain inflammation.

Amino Acid Chloromethyl Ketones↗
PubMedDate not supplied

Improved determination of mercury complex with Thiomicher's ketone by beta-correction spectrophotometry.

Determination of the mercury complex formed with Thiomicher's ketone (TMK) was improved by beta-correction spectrophotometry in the presence of a nonionic surfactant at pH 5. The complex formed was Hg(TMK)2, and its true molar absorptivity is reported for the first time: epsilon Hg(TMK)2(560) = 1.04 x 10(5) L/mol.cm. In addition, the stability constant of Hg(TMK)2 was equal to 3.64 x 10(10) at an ion strength of 0.01 at 20 degrees C. Results from analyses of wastewater samples showed that the relative standard deviations were < or = 8.3%, and the recoveries of mercury ranged from 90 to 110%.

Chelating Agents↗