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L J Gaydos

Publications and source records attributed to L J Gaydos.

9 recordsLinked to original sources
PubMed1997

Tetrandrine inhibits signal-induced NF-kappa B activation in rat alveolar macrophages.

Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from a natural Chinese herbal medicine. While this alkaloid has been shown to exhibit antifibrotic and anti-inflammatory activities, its mechanism of action is unknown. The present study was designed to investigate the inhibitory effect of tetrandrine on NF-kappa B activation in the alveolar macrophage. Three different provocative stimuli were used to activate NF-kappa B in these cells. The results indicate that tetrandrine can inhibit the activation of NF-kappa B and NF-kappa B-dependent reporter gene expression by LPS, PMA, and silica in a dose-dependent manner. In contrast, at the doses used, tetrandrine did not interfere with Sp-1 DNA binding activity or Sp-1-dependent reporter gene expression in these cells. Western blot analysis suggests that the inhibitory effect of tetrandrine on NF-kappa B activation can be attributed to its ability to suppress signal-induced degradation of I kappa B alpha, a cytoplasmic inhibitor of the NF-kappa B transcription factor.

Alkaloids↗
PubMed1997

Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages.

The role of nuclear factor (NF)-kappaB transcription factor in silica-induced cyclooxygenase (COX) II gene expression was examined in the rat alveolar macrophage cell line NR8383. Our results indicate that NF-kappaB can be activated in this cell line by silica exposure. Suppression of NF-kappaB activation in these cells leads to an attenuation of COX II mRNA accumulation induced by silica. Using an electrophoretic mobility shift assay and a reporter gene assay, we provide evidence that at least two kappaB sites in the 5'-flanking region of the rat COX II gene are involved for silica-induced transcriptional control of the COX II gene. The first motif, -404 GGGGATTCCC -395, is absolutely conserved in sequence and is localized in a similar position among the COX II genes found in humans, rats, and mice. The second motif, -91 GGGGAAAGCC -82, was conserved only in the mouse and rat COX II genes in sequence and in location. Aspirin, a COX inhibitor, was shown to suppress silica-induced NF-kappaB activation. However, prostaglandin E2, one of the important downstream reaction products catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-kappaB activation by retarding the degradation of silica-induced inhibitor NF-kappaB. These results suggest that an interdependent regulation may exist between NF-kappaB activation and COX or its products.

Animals↗
PubMed1996

Induction of nitric oxide and nitric oxide synthase mRNA by silica and lipopolysaccharide in PMA-primed THP-1 cells.

Nitric oxide (NO), a nitrogen-free radical, plays an important role in mediating inflammatory reaction and cytotoxicity of tissue. To determine whether NO was involved in silica-induced pulmonary tissue damage, we studied the effects of silica on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression by THP-1 cells, a monocyte-like cell line with properties of the pulmonary alveolar macrophage. Experimental results showed that silica elicited a marked stimulation of nitric oxide production in a time-dependent manner by THP-1 cells in vitro following the priming of these cells with the phorbol ester PMA. Both nitric oxide synthase inhibitor N-monomethyl-L-arginine (NMMA) and xanthine oxidase inhibitor allopurinol can partially suppress silica-induced NO production in PMA-primed THP-1 cells. Northern blot analysis indicated that, after 2 h of silica exposure, PMA-primed THP-1 cells began to express iNOS mRNA, which reached peak expression at 8 h. Endotoxin treatment of these cells produced a similar effect. These results indicated that silica is a potent inducer of NO production in macrophages and its ability to induce tissue damage may partially be attributed to its ability to initiate excessive production of nitric oxide from macrophages.

Allopurinol↗
PubMed1995

Dependence and reversal of nitric oxide production on NF-kappa B in silica and lipopolysaccharide-induced macrophages.

In this report the differential regulation of NF-kappa B and nitric oxide (NO) was investigated in the mouse macrophage cell line RAW 264.7 following exposure to a mineral dust (silica) and/or an endotoxin (Lipopolysaccharide, LPS). The results indicated that silica and LPS can significantly induce the activation of NF-kappa B as well as elicit enhanced production of NO in RAW 264.7 cells as part of an early inflammatory response mechanism. A 24-hour time-course study showed that NO release from these cells continued to increase following the initial stimulus by LPS or silica. In contrast, activation of NF-kappa B was maximal at 6 hours and then showed a steady decline to 24 hours. The production of NO was suppressed by protease inhibitor and antioxidant, both of which block the activation of NF-kappa B. Surprisingly, the use of an NO synthase inhibitor resulted in an enhancement of NF-kappa B activation. These findings suggest that NO produced in macrophage cells in response to an inflammatory stimulus like silica or LPS my be linked to a negative feedback role on the activation of NF-kappa B.

Acetylcysteine↗
PubMed1995

Essential role of NF-kappa B activation in silica-induced inflammatory mediator production in macrophages.

In this report, we demonstrate that NF-kappa B, a ubiquitous transcription factor, plays an essential role in silica-induced inflammatory mediator production in the mouse macrophage cell line RAW 264.7. Compared to the effect of lipopolysaccharide (LPS), silica mediated a stronger activation of NF-kappa B p50/p50 homodimer at early phase of poststimulation. Furthermore, activation of NF-kappa B by silica and LPS appears to be mediated by different signal transduction pathways. Both silica and LPS increased mRNA expression in these cells for cyclooxygenase II, inducible nitric oxide synthase, tumor necrosis factor-alpha and interleukin-1 alpha. This expression was attenuated along with the inhibition of NF-kappa B activation.

Animals↗
PubMed1995

Inflammatory and fibrotic mediator release by alveolar macrophages from coal miners.

Eicosanoids and cytokines produced by alveolar macrophages (AM) are key mediators of pulmonary inflammation and fibrosis. In order to determine if eicosanoid production and cytokine production are altered in AM obtained from coal miners, we compared production of prostaglandin E2 (PGE2), thromboxane A2 (TXA2), leukotriene B4 (LTB4), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) by cultured AM from normal human subjects and coal miners. The recovery of AM from miners' lungs by bronchoalveolar lavage was significantly greater than that from control subjects. Mean eicosanoid and cytokine production by AM from active miners was also increased compared to AM from control subjects, but this increase was not statistically significant. AM from control subjects produced significantly more TXA2 and TNF alpha when exposed to lipopolysaccharide than did AM from miners. The cyclooxygenase inhibitor suprofen reduced PGF2 and TXA2 production and TNF alpha release but had no effect on LTB4 production of IL-1 beta release by miners' AM. The lipoxygenase inhibitor nordihydroguaiaretic acid attenuated TNF alpha release, as well as that of LTB4, but had no effect on IL-1 beta release. Inhibition of thromboxane synthase by UK 38,485 also reduced TNF alpha release by active miners' AM but had no effect on PGE2, LTB4 production, or IL-1 beta release. The results of these studies suggest that occupational inhalation of coal dust may increase total lung eicosanoid and cytokine levels and reduce the reactivity of AM to bacterial endotoxin. Furthermore, coal dust-induced changes in both eicosanoid and cytokine release may be subject to pharmacological modulation.

Adult↗
PubMed1993

An inhibitor of thromboxane production attenuates tumor necrosis factor release by activated human alveolar macrophages.

Tumor necrosis factor alpha (TNF alpha) and thromboxane A2 (TXA2) are major products of the activated alveolar macrophage and serve as key mediators of lung injury. In order to determine if the synthesis of TXA2 and the release of TNF alpha are associated, the production of these inflammatory agents by the human alveolar macrophage (AM), as a result of activation by lipopolysaccharide (LPS), was assessed in the absence and presence of the thromboxane synthase inhibitors UK 38,485 (Dazmegrel) and OKY 046. UK 38,485 and OKY 046 inhibited both LPS-stimulated TXA2 production and TNF alpha release in a dose-dependent manner. Prostaglandin E2 (PGE2) production was not increased by UK 38,485 or OKY 046. Neither LPS nor UK 38,485 had any effect on LTB4 production by AM. Neither UK 38,485 or OKY 046 had any effect on LPS-stimulated interleukin-1 beta release. However, the TXA2 mimetic, U46619, did not stimulate TNF alpha release by AM either in the absence or presence of UK 38,485. These findings suggest that 1) UK 38,485 and OKY 046 are inhibitors of both TXA2 production and TNF alpha release by activated human AM, 2) UK 38,485 probably does not exert its inhibitory action on TNF alpha release through effects on eicosanoid production and 3) the possibility that TNF alpha- and TXA2-induced lung injury may be subject to amelioration by imidazole-based compounds should be further evaluated.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMedDate not supplied

Loose-coupling a cellular automaton model and GIS: long-term urban growth prediction for San Francisco and Washington/Baltimore.

"Prior research developed a cellular automaton model, that was calibrated by using historical digital maps of urban areas and can be used to predict the future extent of an urban area. The model has now been applied to two rapidly growing, but remarkably different urban areas: the San Francisco Bay region in California and the Washington/Baltimore corridor in the Eastern United States. This paper presents the calibration and prediction results for both regions, reviews their data requirements, compares the differences in the initial configurations and control parameters for the model in the two settings, and discuses the role of GIS in the applications."

Americas↗