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V Jankovic

Publications and source records attributed to V Jankovic.

12 recordsLinked to original sources
PubMed2001

STAT1 is required for iNOS activation, but not IL-6 production in murine fibroblasts.

The role of transcription factor STAT1 in production of pro-inflammatory mediators nitric oxide (NO) and IL-6 was examined in murine embryonic fibroblasts. While cells from wild-type animals released large amounts of NO after stimulation with IFN-gamma in combination with LPS, TNF-alpha or IL-1, their STAT1-deficient counterparts failed to synthesise detectable levels of this free radical gas. Inability of STAT1-/- fibroblasts to produce NO was accompanied by complete absence of mRNA for iNOS and its transcription factor IRF-1, both readily upregulated in wild-type cells. However, treatment with cytokines (IFN-gamma, TNF-alpha, IL-1, IL-17) significantly increased IL-6 generation in STAT1-deficient fibroblasts. These results indicate that STAT1 activation and subsequent IRF-1 transcription are required for induction of iNOS, but not IL-6 in murine fibroblasts.

Animals↗
PubMed2001

Pentoxifylline inhibits the synthesis and IFN-gamma-inducing activity of IL-18.

The effect of phosphodiesterase-inhibiting anti-inflammatory drug pentoxifylline (PTX) on LPS-induced IL-18 synthesis and IL-18-mediated IFN-gamma-induction were investigated. In a dose-dependent manner PTX inhibited production of IL-18 in LPS-treated cultures of murine spleen cells and bone marrow-derived macrophages. Similarly, PTX treatment significantly reduced blood IL-18 levels and expression of spleen IL-18 mRNA in LPS-challenged mice. The inhibitory effect of PTX was specific for IL-18, since LPS-induced IL-12 p40 release was not suppressed either in splenocyte cultures or blood of LPS-injected animals. Synergistic induction of IFN-gamma by combined IL-12/IL-18 treatment was also inhibited by PTX in vitro and in vivo. Experiments with IL-12 pretreatment of splenocytes, followed by IL-18 stimulation, revealed that PTX suppressed both IL-12 and IL-18 signals responsible for IFN-gamma induction. These results suggest that interference with IL-18 synthesis and IFN-gamma-inducing activity might contribute to anti-inflammatory actions of PTX.

Animals↗
PubMed2000

Differential regulation of nitric oxide production by increase of intracellular cAMP in murine primary fibroblasts and L929 fibrosarcoma cell line.

The effect of intracellular cAMP rise on nitric oxide (NO) production was compared in murine primary fibroblasts isolated from the spleens of CBA mice, and L929 fibrosarcoma cell line. Treatment of confluent L929 cells with cAMP analogues -dibutyryl-cAMP (db-cAMP) or 8-Cl-cAMP caused dose-dependent augmentation of inducible NO synthase (iNOS)-mediated NO production, which has been abrogated by inhibition of protein synthesis with cycloheximide or addition of selective iNOS inhibitor aminoguanidine. In contrast, under the same cultivating conditions, cAMP analogues were not able to upregulate NO synthesis in primary fibroblasts. Treatment with cAMP analogues or non-selective phosphodiesterase (PDE) inhibitor pentoxifylline affected IFNgamma-induced NO synthesis in both cell types, but in the opposite manner-enhancing in L929 cells and suppressive in primary fibroblasts. The induction of iNOS, but not its catalytic activity, was impaired in cAMP-treated primary fibroblasts. Finally, PDE type IV inhibitor rolipram enhanced IFN-gamma-triggered NO synthesis in L929 cells, but was unable to mimic cAMP analogue or PTX-mediated suppression of NO synthesis in spleen fibroblasts. These results suggest that, in contrast to L929 fibrosarcoma cell line, intracellular cAMP rise might have a role in downregulation of NO production in murine primary fibroblasts.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Cell-specific inhibition of inducible nitric oxide synthase activation by leflunomide.

The influence of a novel immunomodulating drug, leflunomide, on iNOS-dependent nitric oxide (NO) production in rodent macrophages and fibroblasts was investigated. Leflunomide's active metabolite A77 1726 caused a dose-dependent decrease of NO production in IFN-gamma-treated L929 fibroblasts. The observed effect was cell-specific, as well as stimulus-specific, since A77 1726 did not affect NO production in IFN-gamma-stimulated murine peritoneal macrophages or db-cAMP-treated L929 cells. A77 1726 reduced expression of IFN-gamma-induced iNOS and IRF-1 mRNA in L929 cells, while iNOS enzymatic activity remained unchanged. Specific inhibitor of MAP kinase kinase (MEK), PD98059, but not unselective protein kinase inhibitor genistein, completely mimicked cell-type-specific and stimulus-specific NO-inhibitory action of leflunomide. Therefore, the recently described inhibition of MEK/MAP pathway by leflunomide could present a possible mechanism for its suppression of iNOS activation in L929 fibroblasts. Finally, a similar inhibitory effect of A77 1726 on both NO production and iNOS mRNA expression was observed also in IFN-gamma + LPS-activated murine and rat primary fibroblasts.

Adjuvants, Immunologic↗
PubMed2000

Cryptococcus neoformans neutralizes macrophage and astrocyte derived nitric oxide without interfering with inducible nitric oxide synthase induction or catalytic activity - possible involvement of nitric oxide consumption.

The effect of Cryptococcus neoformans on the accumulation of nitrite, an indicator of nitric oxide (NO) synthesis, was investigated in cytokine (interferon-gamma [IFN-gamma] and interleukin [IL]-1)-stimulated cultures of rat peritoneal macrophages and C6 astrocytoma cells. Cytokine-induced nitrite generation in cultures of both cell types was inhibited in a dose-dependent manner by live C. neoformans, but not by heat-killed cryptococcal cells or conditioned medium from yeast cultures. C. neoformans-mediated reduction of nitrite formation coincided with impairment of NO-dependent macrophage tumoricidal activity. Cytokine-triggered induction of inducible NO synthase (iNOS) was unaffected in C6 cells, and only marginally reduced in macrophages. When cells were pretreated with cytokines for 24 h to induce iNOS, and any further induction was prevented by inhibition of protein synthesis, C. neoformans was still able to reduce nitrite accumulation in cultures of both cell types. Finally, live C. neoformans, but not heat-killed yeast cells or yeast culture supernatant, significantly reduced nitrite production in a culture solution of NO-releasing compound S-nitrosoglutathione (GSNO). Thus, it appears that cryptococcal reduction of nitrite formation in macrophage and C6 cultures was caused by the consumption of NO by some yeast molecule, rather than by the inhibition of cellular NO synthesis.

Animals↗
PubMed1996

Combination warp-matching method for stereotactic neurosurgery.

Digital image warping is a growing branch of image processing that deals with geometric transformation techniques. A geometric transformation is an operating that redefines the spatial relationship between points in an image. Physically based modeling is a field strongly attracting research interest in recent years. A physically based model includes physical characteristics of things being modeled and specifies their behavior via mathematical equations. This paper presents a warp-matching method and a general non-rigid body representation suitable for physically based modeling of deformations of heterogeneous objects. The main aim is to develop a new heterogeneous warping technique to correct for distortion in medical data sets.

Humans↗
PubMed1994

Transformation of computed tomography and magnetic resonance images.

This paper discusses the transformation of computed tomography (CT) and magnetic resonance (MR) images, which maps the stereotactic volumetric cube of one examination to another. There are some mathematical problems connected with the present method. This approach provides a better visual detection and localization of the target point for the neurosurgeon or radiologist.

Humans↗