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Dive into the research topics where Agnieszka Grabowska is active.

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Featured researches published by Agnieszka Grabowska.


Journal of Leukocyte Biology | 1995

Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators.

Janusz Marcinkiewicz; Agnieszka Grabowska; Joanna Bereta; Teresa Stelmaszynska

Taurine (Tau) is an exceptionally abundant free amino acid in the cytosol of inflammatory cells and especially in neutrophils. Taurine protects cells from self‐destruction during processes that generate oxidants. The major function of Tau in leukocytes is to trap chlorinated oxidants (HOCl). Taurine reacts with HOCl to produce the long‐lived compound taurine chloramine (TauCl). Previously, we have shown that other products of the neutrophil chlorinating system are able to modify functions of macrophages. In this study, we investigated in vitro the influence of TauCl on the generation of inflammatory mediators by activated macrophages. We have found that TauCl inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor α, and interleukin‐6, but TauCl slightly enhanced the release of IL‐1α. The formation of nitrites by interferon‐γ‐activated macrophages was inhibited by TauCl in a dose‐dependent manner. Taurine chloramine also reduced the level of inducible nitric oxide synthase (iNOS) mRNA in macrophages, in a similar concentration‐dependent manner. Although our experiments do not exclude a direct effect of TauCl on enzymatic activity of iNOS, the inhibition of iNOS expression seems to be the major mechanism responsible for suppression of NO formation. Finally, we discuss the biological role of TauCl in vivo. We suggest that at the site of inflammation TauCl works as a specific signaling molecule of activated neutrophils that coordinates the generation of inflammatory mediators in macrophages.


Immunopharmacology | 1998

Taurine chloramine down-regulates the generation of murine neutrophil inflammatory mediators

Janusz Marcinkiewicz; Agnieszka Grabowska; Joanna Bereta; Krzysztof Bryniarski; Bernadeta Nowak

We previously reported that taurine chloramine (TauCl), a product of activated neutrophils, inhibits the generation of macrophage inflammatory mediators such as nitric oxide (NO), TNF-alpha, and PGE2. Taurine, the most abundant free amino acid in the cytosol of neutrophils, is chlorinated to form TauCl by the halide-dependent myeloperoxidase (MPO) system. Under physiological conditions, TauCl reduces HOCl toxicity. In this study, we investigated the influence of TauCl on generation of oxygen free radicals, cytokines and eicosanoids by activated murine peritoneal neutrophils. We found that TauCl, but not taurine alone, inhibited the production of NO, prostaglandin E2, interleukin-6 and tumor necrosis factor-alpha, in a dose-dependent manner. In contrast, the products of the respiratory burst, as measured by luminol-dependent chemiluminescence (LCL), were reduced by both taurine and TauCl. However, taurine affected LCL at higher concentrations and to a lesser extent than TauCl. The results of these studies suggest that TauCl decreases production of tissue-damaging inflammatory mediators and may regulate the balance between protective, microbicidal and toxic effect of neutrophils.


Immunology | 1999

Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase-halide system

Janusz Marcinkiewicz; Bernadeta Nowak; Agnieszka Grabowska; Małgorzata Bobek; L. Petrovska; Benjamin M. Chain

Taurine chloramine (TauCl) is a major chloramine generated in activated neutrophils as a result of the reaction of highly toxic hypochlorous acid and taurine, the most abundant free amino acid in cytosol. In this study we have tested the influence of TauCl on the properties of murine dendritic cells (DC), the major cell population involved in the initiation of an adaptive immune response against pathogenic organisms. N418+, MHC II+, B7‐2+ dendritic cells, generated from the mouse bone marrow cells cultured in the presence of granulocyte–macrophage colony‐stimulating factor, were stimulated by interferon‐γ and lipopolysaccharide to produce nitric oxide, reactive oxygen species, interleukin‐6 (IL‐6), tumour necrosis factor‐α, and IL‐12, in the presence of different doses of TauCl. TauCl differently inhibited the generation of these inflammatory mediators in a dose‐dependent manner. Furthermore, TauCl selectively modulated the ability of DC to induce the release IL‐2 and IL‐10 from T cells. These results suggest that neutrophil‐derived mediators, such as TauCl, at a site of inflammation, may affect the functions of sentinel DC and macrophages, and play a role in maintaining the balance between the inflammatory response and the induction of an antigen‐specific immune response.


Inflammation Research | 2000

Antimicrobial and cytotoxic activity of hypochlorous acid: interactions with taurine and nitrite

Janusz Marcinkiewicz; Benjamin M. Chain; Bernadeta Nowak; Agnieszka Grabowska; Krzysztof Bryniarski; J. Baran

Objective. HOCl, a major bactericidal product of neutrophil MPO - halide system reacts with taurine to form taurine chloramine (TauCl), a less toxic anti-inflammatory mediator. Recently, it has been reported that HOCl may also react with nitrite (NO2-), a major end-product of nitric oxide (NO) metabolism, to form very active oxidant, nitryl chloride (NO2Cl). The present study was conducted to elucidate the effect of nitrite on bactericidal and some immunoregulatory properties of HOCl and TauCl.¶Materials: TauCl was prepared from NaOCl and taurine. The reaction was carried out at pH 5.0 and pH 7.4, in the presence or absence of nitrite. All reactions were monitored by UV absorption spectra.¶Methods: Bactericidal activity of HOCl and TauCl in the presence of nitrite was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the effect of the compounds on activity of inflammatory cells, murine peritoneal neutrophils (PMN) and macrophages were used. The cells were activated in vitro with either LPS, IFN-γ or zymosan and the production of following mediators was measured: reactive oxygen species using luminol-dependent chemiluminescence; nitric oxide by Griess reaction; TNF-α using capture ELISA. In addition, we tested the effect of HOCl and TauCl on activity of myeloperoxidase (MPO).¶Results: At physiological pH nitrite reacts with HOCl but not with TauCl. This reaction was abolished in the presence of taurine. Nitrite prevented HOCl-mediated bacterial killing, inhibition of MPO activity, cellular cytotoxicity and inhibition of TNF-α Production. Nitrite did not affect any activity of TauCl.¶Conclusion: We have shown that nitrite may react in vitro with HOCl but not with TauCl, to form new biologically active product(s). We did not confirm the hypothesis that a product of HOCl reaction with nitrite is more toxic than HOCl. To the contrary, we found that nitrite diminished bactericidal and immunoregulatory properties of HOCl. In vivo, nitrite will also compete with taurine for reaction with PMN-released HOCl. Nevertheless, due to high concentration of taurine in PMN cytosol, formation of TauCl will be a major regulatory mechanism of MPO-halide-system.


Arthritis & Rheumatism | 1999

Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast‐like synoviocytes

Ewa Kontny; Agnieszka Grabowska; Jacek Kowalczewski; Mariola Kurowska; Iwona Janicka; Janusz Marcinkiewicz; Włodzimierz Maśliński

OBJECTIVE To examine whether taurine (Tau) or its physiologic chlorinated derivative, taurine chloramine (Tau-CI), affects proliferation of, and proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) production by, fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients. METHODS FLS, isolated from the synovial tissue of 19 RA patients and cultured in vitro for 3-6 passages, were stimulated with the recombinant human cytokines IL-1beta (1 ng/ml), tumor necrosis factor alpha (TNFalpha; 10 ng/ml), or IL-17 (10 ng/ml) in the presence of either Tau or Tau-Cl, which were added at concentrations of 50-500 microM. Tau and Tau-Cl were added simultaneously with, 2 hours before, or 24 hours after the stimuli. The concentrations of IL-6 and IL-8 were determined in culture supernatants using specific enzyme-linked immunosorbent assays. Proliferation of FLS was estimated on the basis of 3H-thymidine incorporation into the cells, which were cultured for 72 hours in the presence of recombinant human basic fibroblast growth factor (bFGF) (1 ng/ml) and Tau or Tau-Cl, which were added simultaneously at the beginning of the culture. RESULTS Cultured in vitro, RA FLS spontaneously secreted low levels of IL-6 and IL-8, but when RA FLS were stimulated with IL-1beta, TNFalpha, or IL-17, significantly higher amounts of IL-6 and IL-8 were produced. Tau-Cl, but not Tau, inhibited cytokine-triggered synthesis of IL-6 (50% inhibitory concentration [IC50] approximately 225 microM) and IL-8 (IC50 approximately 450 microM) when added simultaneously with the stimuli. However, IL-17-induced production of IL-8 was not affected by Tau-Cl. In the cells prestimulated with IL-1beta for 24 hours, Tau-Cl still inhibited synthesis of IL-6, but did not affect IL-8 production. Moreover, Tau-Cl inhibited spontaneous and bFGF-triggered proliferation of FLS in a dose-dependent manner. Neither Tau nor Tau-Cl affected cell viability. CONCLUSION The results of these studies demonstrate that Tau-Cl inhibits production of proinflammatory cytokines by RA FLS, as well as proliferation of these cells. Thus, Tau-Cl may act as a physiologic modulator of FLS functions related to their pathogenic role in RA.


Immunopharmacology | 2000

Differential effects of pentoxifylline, a non-specific phosphodiesterase inhibitor, on the production of IL-10, IL-12 p40 and p35 subunits by murine peritoneal macrophages

Janusz Marcinkiewicz; Agnieszka Grabowska; Ryszard Lauterbach; Małgorzata Bobek

Pentoxifylline (PTX), a methylxanthine derivative, has been reported to be an effective drug in inhibiting TNF-alpha responses during septic shock. The inhibition of TNF-alpha production seems to be correlated with increased intracellular cAMP levels. PTX also affects the production of other cytokines such as IL-1, IL-6, IL-10, IL-12, and IFN-gamma. However, inhibition, as well as enhancement of cytokine production, has been observed in vitro, depending on the PTX concentration and cell type used.IL-12 is a heterodimeric cytokine that plays an important role in the development of Th1-mediated inflammatory responses. IL-12 along with TNF-alpha and other proinflammatory cytokines has shown to be responsible for the pathological reaction, which may lead to septic shock. For biological activity, the expression of both subunits of IL-12, p35 and p40, is required. Moreover, the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In this study, we investigated the effects of PTX on the production of both proinflammatory (TNF-alpha, IL-6, IL-12) and anti-inflammatory (IL-10) cytokines by murine macrophages (Mφ). We have found that PTX, at concentrations below 100 microg/ml, selectively inhibited the production of TNF-alpha. Forskolin, a cAMP-elevating agent, similarly affected the production of the cytokines tested. However, at higher concentrations, PTX inhibited the production of TNF-alpha, IL-10, and IL-12 p35, but surprisingly, PTX enhanced the production of IL-12 p40. Concentrations of IL-10 were negatively correlated with the concentrations of IL-12 p40 subunit. These results further confirm the relevance of the use of PTX in clinical trials of immunological disorders characterised by inappropriate Th1 type immune responses.


Immunology | 1998

Modulation of antigen-specific T-cell activation in vitro by taurine chloramine.

Janusz Marcinkiewicz; Agnieszka Grabowska; Benjamin M. Chain

Taurine chloramine (TauCl) is produced during inflammation by reaction of hypochlorous acid (HOCl) with taurine, the most abundant free amino acid in neutrophils. We previously reported that TauCl inhibits the generation of macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2),tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). In this study, the activity of TauCl in modulating T‐cell activation was investigated. Treatment of T cells with TauCl (0·1–0·3 mm), prior to activation, was found to inhibit interleukin‐2 (IL‐2) release in response to both mitogen and antigen stimulation. Similarly, pretreatment of A‐20 antigen presenting cells (APCs), at low cell numbers, was found to inhibit their ability to process and present ovalbumin (OVA) to a specific T‐cell hybridoma. In contrast, pretreatment of higher numbers of A‐20 cells with TauCl in the presence of OVA enhanced subsequent presentation of OVA. Finally, OVA modified with TauCl was processed and presented more efficiently than native VA. Thus, TauCl is able to modulate induction of a specific adaptive immune response at several independent points of the overall antigen‐presenting pathway.


Immunology | 1997

Enhancement of CD4+ T-cell-dependent interleukin-2 production in vitro by murine alveolar macrophages: the role of leukotriene B4.

Janusz Marcinkiewicz; Agnieszka Grabowska; K. Bryniarski; Benjamin M. Chain

Local tissue macrophages are known to play a key role in regulation of adaptive immune responses, often by inhibition of T‐cell activation and proliferation. In this study, we compare the influence of alveolar and peritoneal macrophages on T‐cell‐dependent interleukin‐2 (IL‐2) release. Alveolar macrophages, in contrast to peritoneal macrophages, enhance IL‐2 release. Assay of a panel of potential macrophage‐derived mediators indicated that activated alveolar macrophages stimulated greater release of IL‐1β, tumour necrosis factor‐α and, especially, leukotriene B4 (>100 times) than activated peritoneal macrophages. Inhibition of prostaglandin synthesis by alveolar macrophages further enhanced the production of IL‐2, while inhibition of leukotriene synthesis abolished the enhancement. The addition of exogenous prostaglandin E2 inhibited IL‐2 release, while exogenous leukotriene B4 enhanced IL‐2 release. When added simultaneously, the two compounds antagonized each other’s activity. In conclusion, this study confirms that alveolar macrophages enhance IL‐2 secretion, and suggests that this enhancement may be due at least in part to the very high rates of production of leukotriene B4. The overall influence of macrophage populations on T cells in vivo will reflect the complex balance between the multiple mediators produced within the local tissue microenvironment.


Neonatology | 1995

Effect of Pentoxifylline on Nitric Oxide Released by Murine Macrophages

Ryszard Lauterbach; Agnieszka Grabowska; Janusz Marcinkiewicz

The growing knowledge on the pathological role of tumor necrosis factor alpha (TNF-alpha) and nitric oxide in septic shock stimulated efforts to control their generation pharmacologically in clinical situations. Pentoxifylline (PTXF) is well known as an inhibitor of TNF synthesis, whereas information about its role in suppression of NO generation is much less available. In our study, we have shown that PTXF suppresses the synthesis of both mediators, TNF and NO, released by macrophages activated with different stimuli. However, in contrast to N-monomethyl-L-arginine (an inhibitor of NO synthase), PTXF influenced NO generation only during the induction phase. In conclusion, we suggest that a possible new therapeutic approach in septic shock may result from the inhibition of these two major mediators by simultaneous application of PTXF and a specific inhibitor of NO generation. Further experimental investigations and clinical trials are necessary to evaluate the safety and effectiveness of application of these inhibitors.


Central European Journal of Biology | 2008

Optimization of a synthetic siRNA delivery for the treatment of rhabdomyosarcoma

Ewa Lesko; Katarzyna Miekus; Agnieszka Grabowska; Aleksandra Gładys; Marcin Majka

Silencing of a target-genes by small interfering RNA (siRNA) has emerged as a powerful new tool not only for basic research but also with potential therapeutic benefits. This paper demonstrates that optimal delivery strategy is crucial for effective target-gene silencing. Using lipofection, under defined conditions, we were able to markedly down-regulate expression of the selected genes involved in rhabdomyosarcoma metastasis: MET, CXCR4, LIFR and PAX3-FKHR.

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Miroslaw Bik-Multanowski

Jagiellonian University Medical College

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Bernadeta Nowak

Jagiellonian University Medical College

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Krzysztof Bryniarski

Jagiellonian University Medical College

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