PI3K-Akt/PKB signaling pathway in neutrophils and mononuclear cells exposed to N-nitrosodimethylamine.

Neutrophils (PMN) play diverse regulatory and effector functions in the immune system through the release of reactive nitrogen species, including nitric oxide (NO). The enzyme responsible for NO synthesis in PMN is inducible nitric oxide synthase (iNOS) that is regulated by various signaling pathways, e.g.

Role of ERK1/2 kinase in the expression of iNOS by NDMA in human neutrophils.

Potential role of ERK1/2 kinase in conjunction with p38 in the regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, and superoxide anion generation by human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was determined. Increased synthesis of NO due to the involvement of iNOS in neutrophils exposed to NDMA was observed. In addition, intensified activation of ERK1/2 and p38 kinases was determined in these cells.

Berberis vulgaris root extract alleviates the adverse effects of heat stress via modulating hepatic nuclear transcription factors in quails.

To evaluate the action mode of Berberis vulgaris root extract in the alleviation of oxidative stress, female Japanese quails (n 180, aged 5 weeks) were reared, either at 22°C for 24 h/d (thermoneutral, TN) or 34°C for 8 h/d (heat stress, HS), and fed one of three diets: diets containing 0, 100 or 200 mg of B. vulgaris root extract per kg for 12 weeks. Exposure to HS depressed feed intake by 8·5% and egg production by 12·1%, increased hepatic malondialdehyde (MDA) level by 98·0% and decreased hepatic superoxide dismutase, catalase and glutathione peroxidase activities by 23·5, 35·4 and 55·7%, respectively (P<0·001 for all).

A proliferation-inducing ligand (APRIL) in neutrophils of patients with oral cavity squamous cell carcinoma.

Available data indicating a role for neutrophils in the tumor-host reactions are controversial. In 37 patients with oral cavity squamous cell carcinoma (OSCC), we investigated the expression of a tumor-promoting, proliferation-inducing ligand (APRIL) molecule by peripheral blood neutrophils isolated from blood samples collected at presentation and three weeks after surgery, and the serum levels of TGF-β in the same samples. Additionally, we investigated the consequences of TLR4 activation by LPS for the synthesis of APRIL by those cells.

Role of AP-1 family proteins in regulation of inducible nitric oxide synthase (iNOS) in human neutrophils.

The aim of the study was to assess the activity of AP-1 family proteins, e.g. Fra-1, Fra-2, JunB, JunD, and FosB, engaged in the regulation of inducible nitric oxide synthase (iNOS) expression and the production of NO by neutrophils (PMN) exposed to N-nitrosodimethylamine (NDMA) xenobiotic.

The effect of N-nitrosodimethylamine (NDMA) on Bax and Mcl-1 expression in human neutrophils.

In the present study we examined a role of pro-apoptotic Bax and anti-apoptotic Mcl-1 proteins, participating in the regulation of intrinsic apoptosis pathway in human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA), the environmental xenobiotic. For the purpose comparison, the same studies were conducted in autologous peripheral blood mononuclear cells (PBMCs). The production of cytochrome c by PMNs was also determined.

Effect of N-nitrosodimethylamine on inducible nitric oxide synthase expression and production of nitric oxide by neutrophils and mononuclear cells: the role of JNK signalling pathway.

In neutrophils (PMN) and mononuclear cells (PBMC), one of the enzymes responsible for nitric oxide (NO) synthesis is inducible nitric oxide synthase (iNOS). Changes in iNOS expression result from various signalling pathways including the mitogen-activated protein kinase (MAPK) pathway activated by endogenic and exogenic factors. N-nitrosodimethylamine (NDMA) is a xenobiotic with widespread occurrence in human environment and has an effect on cells of the immune system.

Induction of expression of iNOS by N-nitrosodimethylamine (NDMA) in human leukocytes.

The aim of this study was to assess the influence of N-nitrosodimethylamine (NDMA) on expression of inducible nitric oxide synthase (iNOS), as well as production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by human neutrophils (PMN) and peripheral blood mononuclear cells (PBMC), and the participation of the p38 MAPK kinase in this process. Furthermore, the ability of neutrophils to release superoxide anion was determined. The influence of N-nitrosodimethylamine on iNOS expression was determined in isolated PMN and PBMC cells from peripheral blood of healthy individuals.

The expressions of intrinsic and extrinsic apoptotic pathway proteins in neutrophils of oral cavity cancer patients: a preliminary study.

Introduction: The biological availability and activity of polymorphonuclear neutrophils (PMNs) are regulated by their short life span, which can be additionally shortened by a malignant process. The signaling pathways leading to apoptotic PMN death are classified in two categories: the intrinsic and the extrinsic. In the present study the expressions of proteins participating in the extrinsic apoptotic pathway (DR5, FADD, caspase-8 activity) and the intensity of apoptosis of PMNs from patients with cancer of the oral cavity were examined.

Role of the p38 MAPK pathway in induction of iNOS expression in human leukocytes.

Inducible nitric oxide synthase (iNOS) is one of the enzymes responsible for NO production in neutrophils (PMN) and in peripheral blood mononuclear cells (PBMC). Several studies have demonstrated that iNOS expression is controlled by a wide group of cytokines which achieve their biological effect through, among others, the activation of the p38 MAPK pathway. The aim of the present study was to define the participation of the p38 MAPK pathway in the induction of iNOS expression and NO production by PMN and PBMC of healthy persons after stimulation of rhIL-15 and rhIL-18.

Ruthenium red protects HepG2 cells overexpressing CYP2E1 against acetaminophen cytotoxicity.

We studied the mechanisms of acetaminophen (APAP) cytotoxicity in HepG2 cells overexpressing cytochrome p4502E1, particularly the role of oxidative/nitrosative stress and ryanodine Ca2+ channel. Cells were grown for 24 h with APAP in the presence or absence of 4-methylpyrazole (4MP), L-arginine methyl ester (L-NAME), superoxide dismutase (SOD), or ruthenium red (RuR). Drug cytotoxicity was also tested in cells pretreated overnight with V-PYRRO/NO.

The release of soluble forms of TRAIL and DR5 by neutrophils of oral cavity cancer patients.

In the present study we examined the release of the soluble form of TRAIL by neutrophils (PMN) derived from patients with oral cavity cancer. Simultaneously, we estimated the ability of PMNs of these patients to release the soluble form of DR5 receptor, a natural regulatory protein of TRAIL. The obtained results were confronted with the serum levels of sTRAIL and sDR5.

The Effect of N-nitrosodimethylamine on TRAIL and DR5 expression in human neutrophils--preliminary study.

The intracellular mechanisms of NDMA-induced apoptosis of neutrophils have not yet been fully understood. The aim of this study was to explain whether the TRAIL/DR5 system is implicated in NDMA-induced apoptosis of human neutrophils. The expression of TRAIL and DR5 was examined, as well as the secretion of sTRAIL and sDR5 by human neutrophils treated with NDMA confronted with intensity apoptosis of these cells.

The influence of human neutrophils on N-nitrosodimethylamine (NDMA) synthesis.

N-nitrozodimethyloamine (NDMA) is a carcinogenic compound that can be formed in vivo. NDMA is synthesized from precursors-amines and nitrosating agents. Nitrosating agents are formed through the reaction of oxide, reactive oxygen species and nitric oxide (NO).

Toll-like receptors types 2 and 6 and the apoptotic process in human neutrophils.

Introduction: Neutrophils (PMN) apoptosis plays an important role in limiting the last phase of inflammatory processes. It is unknown whether Toll-like receptor (TLR)2 acts independently or together with TLR6 in this process.

Materials And Methods: The aim of this study was to estimate the relationship between the expressions of TLR2 and TLR6 and the apoptosis of human neutrophils in physiological conditions.

The effect of ethanol and nitric oxide on the N-nitrosodimethylamine formation in HepG2 cells overexpressing CYP2E1.

The influence of lipopolysaccharide (LPS) and the nitric oxide synthase (iNOS) inhibitor--N-nitro-L-arginine methyl ester (L-NAME)--on the formation of N-nitrosodimethylamine (NDMA) by HepG2 cells, engineered to overexpress CYP2E1, was assessed and compared with data from empty vector-transfected cells. HepG2 cells produced significant amounts of NDMA but its levels in the culture media of cells overexpressing CYP2E1 was significantly lower than in empty-vector transfected cells. LPS increased the formation of NDMA, the expression of the iNOS and the production of the nitric oxide (NO).

VEGF, IL-18 and NO production by neutrophils and their serum levels in patients with oral cavity cancer.

It is known that the relationship between pro-angiogenic and anti-angiogenic factors is responsible for the presence and intensity of neoangiogenesis. The angiogenic factors are produced by tumour cells and/or by tumour-infiltrating inflammatory cells such as macrophages or polymorphonuclear leukocytes (PMN). In the present study we compared VEGF secretion with IL-18 and NO release by PMN derived from oral cavity cancer patients.