Biomedical subjects

Natalia Lewkowicz

Publications and source records attributed to Natalia Lewkowicz.

8 recordsLinked to original sources

PubMed2006

Lipopolysaccharide-activated CD4+CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death.

CD4+CD25+ T regulatory (Treg) cells play a central role in the suppression of immune response and prevention of autoimmune reactions. Pathogen recognition receptors expressed by immune cells, such as TLRs, may provide a critical link between the innate and adaptive immune systems. There is also evidence that TLR ligands can directly modulate the suppressive capacity of Treg cells. Here, we showed that CD4+CD25+ Treg cells affect neutrophil function and survival and that the TLR4 ligand is involved in the regulation of the cell interactions. We found that LPS-activated Treg cells inhibit reactive oxygen intermediates and cytokine production by neutrophils. Moreover, Treg cells reverse LPS-induced survival of neutrophils and promote their apoptosis and death. We also found that TCR-activated Treg cells induce the same effects on polymorphonuclear neutrophils as those achieved by TLR4 stimulation. Importantly, the suppressive potential of CD4+CD25+ Treg cells induced by LPS seems to be partially IL-10 and TGF-beta dependent, whereas anti-CD3/CD28 stimulation is rather contact dependent. Together, these observations suggest that Treg cells have the ability to directly regulate neutrophil function and life span when both types of the cells are exposed to LPS.

Apoptosis↗

PubMed2006

[Biological action and clinical application of shark liver oil].

Fish oils contain several active compounds that modify cell activity and influence various functions of the body. Shark liver oils are rich in alkylglycerols and squalene, but contain relatively low amounts of n-3 polyunsaturated fatty acids. Alkylglycerols may control immune response possibly throw modification of platelet activating factor (PAF) and diacylglycerol (DAG) production. Squalene enhances antigen presentation and induction of inflammatory response. Moreover, alkylglycerols and squalene have antitumour activity, that is possibly based on different mechanisms, ie., induction of apoptosis of neoplastic cells, suppression of signal transduction, inhibition of angiogenesis and promoting of transmembrane transport of cytotoxic agents. Shark liver oil has been found to be useful in treatment of conditions resulted from inadequate immune response, and in adjunctive treatment of several types of cancer.

Animals↗

PubMed2005

Epidermal growth factor enhances TNF-alpha-induced priming of human neutrophils.

The intensity of neutrophil inflammatory response could be rapidly amplified by priming with pro-inflammatory mediators such as TNF-alpha, GM-CSF or LPS at low concentrations prior to stimuli. We proposed that epidermal growth factor (EGF) increases TNF-alpha-induced priming of human neutrophils. This study showed that EGF enhanced TNF-alpha-induced activation of neutrophils functions. The addition of EGF to neutrophils cultured with TNF-alpha resulted in increased respiratory burst and phagocytic activity of polymorphonuclear leukocytes (PMN) and up-regulation of adhesion molecule CD11b. Moreover, EGF enhanced IL-8 production by TNF-alpha-primed PMN. EGF alone was able to prime CD11b expression and IL-8 production by PMN. EGF receptor selective tyrosine kinase inhibitor, tyrphostin AG-1517, blocked the effect of priming with EGF, whereas the status of non-primed and TNF-alpha-primed neutrophils remained unaffected. EGFR expression on neutrophils was confirmed by flow cytometry and CELISA methods. These data provide the original evidence that EGF significantly enhances TNF-alpha-induced priming of human neutrophils acting through EGFR tyrosine kinase pathway. The observed effect may be a result of co-operative action of EGF, TNF-alpha and reactive oxygen intermediates (ROI).

CD11b Antigen↗

PubMed2005

Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations.

Recurrent aphthous ulcerations (RAU) are a chronic inflammatory disease with evidence of inappropriate immune response. Previous studies have suggested cell-mediated activation of immune response towards common micro-organisms of oral cavity in RAU. In this investigation, we explored cytokine production by peripheral blood mononuclear cells (PBMC) and T regulatory cell population in blood of active and remission RAU patients as crucial factors for maintenance of peripheral tolerance. Ten patients with minor RAU and 12 healthy individuals were selected for the study. Cytokine levels were analysed in supernatants using Cytometric Bead Array Kit for flow cytometry and ELISA. We have demonstrated increased production of Type 1 cytokines IL-2, IFN-gamma and TNF-alpha as well as IL-5, IL-6 and IL-8 by peripheral blood mononuclear cells in RAU. In contrast, IL-10 and TGF-beta anti-inflammatory cytokine production was decreased in RAU patients compared to healthy individuals. Moreover, we have found that CD4(+)CD25(+high) T regulatory cell proportion was decreased in RAU and represented 3.58+/-0.654% of CD4(+) T cells in active RAU, 4.66+/-0.561% of CD4(+) T cells in remission RAU, whereas in healthy controls CD4(+)CD25(+high) T cells represented 7.30+/-1.238% of CD4(+) T cells (p<0.001). Thus, the obtained results indicate that disproportion in cytokine production may be contributing factor in the pathogenesis of RAU. Alteration in the number of CD4(+)CD25(+high) T regulatory cells in RAU may additionally influence the development of the disease. We propose that imbalance in pro- and anti-inflammatory cytokine network may lead to the breakdown of peripheral tolerance in RAU and the excessive immune response towards harmless micro-organisms colonized oral mucosa or self-antigens.

Adult↗

PubMed2005

[CD4+CD25+ T regulatory cells: their physiology and role in modulating immune response].

Understanding the role of immune system homeostatic balance is crucial for a better understanding of the pathogenesis of many diseases. The efficient regulation of immune response has been recently investigated in numerous studies that emphasize the important role of CD4+CD25+ regulatory T cells. These regulatory cells suppress the proliferation and cytokine secretion of effector cells directly via cell-cell contact and probably indirectly via TGF-beta. This makes T regulatory cells responsible for the control and suppression of inappropriate immune response to self antigens. Moreover, CD4+CD25+ regulatory T cells have an important function in the immunopathology of cancer, allotransplantion, and allergy. Based on murine and human studies, this review presents a characterization of the origin, phenotype, and function of CD4+CD25+ regulatory T cells. In addition, we show a hypothetical mode of the in vivo action of regulatory T cells, which play a central role in maintaining immune homeostasis.

Animals↗

PubMed2005

[CD4+CD25+ T regulatory cells in pathophysiology and therapy of immunologic diseases].

Naturally arising CD4+CD25+ T regulatory cells actively maintain immunological tolerance to self and non-self antigens. Treg cells inhibit proliferative response and cytokine production by effector cells, basically via cell-cell contact. Deficiency or dysfunction in these cells may result in autoimmune diseases. Treg cells may also influence the outcome of infection, cancer, transplantation, allergy, and even some forms of infertility. Enhancement or blockade of natural Treg cells may represent a therapeutic approach to many immunopathologies. However, Treg cells act like a 'double-edged sword', which is why all therapeutic manipulation of these cells on humans should be done with great caution.

Animals↗

PubMed2005

[Effect of high doses of shark liver oil supplementation on T cell polarization and peripheral blood polymorphonuclear cell function].

Fish oils supplementation has been recently widely used in prevention and treatment of the diseases in humans. Fish oil beneficial effects have been investigated in a number of animal disease models as well as human studies. Here, we examined clinical, immunological and biochemical effects of shark liver oil supplementation in high doses in 13 volunteers. The experiment was based on the consumption of 3.6 g of squalene, 3.6 g of alkylglycerols and 750 mg of n-3 polyunsaturated fatty acids (PUFA) per day for 4 weeks. We have shown the increased response of neutrophils towards bacteria, the increased level of C4 component of complement in blood, the rise of total antioxidant status of serum, and the predominance of Type I cytokine IFN-gamma, TNF-alpha and IL-2 production by peripheral blood mononuclear cells after shark liver oil intake. Moreover, shark liver oil supplementation markedly affect lipid metabolism and cholesterol balance. The increase of total cholesterol level from 182.92 +/- 29.290 mg/dl before oil consumption to 224.46 +/- 62.198 mg/dl after diet rich in oil, and the decrease of HDL fraction were noted. However, metabolism of lipids normalised spontaneously after the end of the experiment in all the individuals. The results of the present study have shown, that the main effects of shark liver oil are the result of the biological activity of squalene and 1-O-alkylglycerols, which dominate in the composition of the oil quantitatively. On the contrary, anti-inflammatory effects of n-3 PUFA do not manifest, when taking together with high doses of squalene and alkylglycerols. On the bases of these observations, we propose that shark liver oil supplementation in high doses is beneficial in bacterial, viral and fungal infections, whereas patients with atherosclerosis or autoimmune diseases should avoid the consumption of high amounts of shark liver oil.

Adult↗

PubMed2003

Innate immune system is implicated in recurrent aphthous ulcer pathogenesis.

BACKGROUND: Recurrent aphthous ulcers (RAU) is a chronic inflammatory disease with evidence of inappropriate immune response. This study presents the status of innate immune system in RAU. METHODS: Twenty RAU patients and 19 healthy individuals were selected. The status of peripheral blood neutrophils (reactive oxygen intermediates (ROI) production, CD11b, TNF-RI and TNF-RII expression), concentration of antioxidants, sTNF-R, C3c, C4 and haemolytic activity of the complement system, as well as mannose-binding lectin (MBL), in the serum of RAU patients in active stage and in remission of the disease were determined. RESULTS: Peripheral blood neutrophils were primed in RAU, which resulted in increased ROI production by resting and fMLP-stimulated neutrophils and diminished ROI production after in vitro priming. The increased expression of CD11b on resting and fMLP-stimulated neutrophils in RAU may also point to their previous in vivo stimulation. The decreased total antioxidant status of serum observed in RAU may be a result of increased ROI production by peripheral blood neutrophils. The levels of C3c, C4 and haemolytic activity of the complement system were higher in RAU than in healthy people. No significant differences between active and remission RAU were noted. CONCLUSION: Presented observations confirm that the innate immune system is involved in RAU pathogenesis.

Adolescent↗