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Janusz Marcinkiewicz

Publications and source records attributed to Janusz Marcinkiewicz.

15 recordsLinked to original sources
PubMed2006

Susceptibility of Propionibacterium acnes and Staphylococcus epidermidis to killing by MPO-halide system products. Implication for taurine bromamine as a new candidate for topical therapy in treating acne vulgaris.

INTRODUCTION: Taurine chloramine (TauCl) and taurine bromamine (TauBr) are the main haloamines produced by activated neutrophils. TauCl exerts both anti-inflammatory and microbicidal activities. Clinical studies showed that TauCl may be useful as an antimicrobial agent in the local treatment of infections. Much less is known about TauBr. Circumstantial evidence suggests that Propionibacterium acnes (PA) has a role in the inflammation of acne. Available topical therapies include antimicrobial agents which reduce total PA numbers and anti-inflammatory agents which suppress activity of the cells present in acne inflammatory lesions. In this study the bactericidal activities of TauBr and TauCl against PA and Staphylococcus epidermidis (SE), as a control strain, were investigated. Moreover, the influence of these haloamines on the generation of reactive oxygen species (ROS) by activated neutrophils was also tested. MATERIALS AND METHODS: TauBr and TauCl were prepared by reaction of taurine with HOBr and HOCl, respectively. The reaction was monitored by UV absorption spectra. The bactericidal activities of TauBr and TauCl were determined by the pourplate method. The generation of ROS by neutrophils was determined by luminol chemiluminescence assay. RESULTS: In our experimental set-up, TauBr showed stronger antibacterial activity than TauCl. Interestingly, PA was significantly more susceptible to TauBr than SE was. Moreover, TauBr at non-cytotoxic concentrations significantly reduced ROS generation by neutrophils. CONCLUSIONS: Since PA is considered to be an etiological agent in acne and ROS are closely correlated with the pathogenesis of inflammatory skin diseases, the reported data suggest that TauBr may be a good candidate for the topical therapy for acne vulgaris.

Acne Vulgaris↗
PubMed2006

Cytotoxicity of taurine metabolites depends on the cell type.

We report that the effect of Tau-Cl on the cell fate strongly depends on the cellular context. In leukemic Jurkat cells Tau-Cl (> 200 microM) triggers mitochondrial, p53-independent apoptosis and amplifies PCD induced by anti-Fas treatment. In contrast, Tau-Cl affects RA FLS in a dose-dependent manner. At the noncytotoxic (200-400 microM) concentrations it induces: (i) p53-dependent growth arrest (Kontny et al., 2005), and (ii) Bax translocation and caspase 9 activity. Although the last events are characteristic for apoptotic state, there is not execution of RA FLS apoptosis, probably due to simultaneous inhibition of caspase 3 activity and prevention of PARP degradation. The last two events suggest an excessive ATP deprivation in Tau-Cl-treated RA FLS. At sufficiently high concentrations (> or = 500 microM) Tau-Cl causes therefore necrosis of these cells. Altogether our results suggest that Tau-Cl is able to eliminate the cells with both functional (RA FLS) and mutated (Jurkat) p53 tumor suppressor. This observation is clinically relevant because Tau-Cl is used in many animal inflammatory models and its sodium salt (used in this study) has been introduced to human therapy (Gottardi and Nagl, 2002; Teuchner et al., 2005).

Animals↗
PubMed2006

Anti-inflammatory effects of taurine derivatives (taurine chloramine, taurine bromamine, and taurolidine) are mediated by different mechanisms.

In this study, in an animal model of zymosan-induced peritonitis we have tested anti-inflammatory properties of Taurolidine (TRD), a synthetic derivative of taurine. In vitro, the effect of TRD and HOCl treated TRD on peritoneal macrophages was compared with that of TauCl. We report that locally administered TRD (Taurolin) shows strong anti-inflammatory properties. TRD inhibits vascular permeability increased by inflammatory stimuli; it also significantly attenuates the influx of neutrophils into the peritoneal cavity, as well as the production of pro-inflammatory cytokines (TNF-alpha, IL-6) by peritoneal exudate cells. Chlorination of TRD resulted in the formation of chloramine (TRD-Cl), as confirmed by characteristic UV spectra. Both TRD and TRD-Cl, more effectively than TauCl, inhibited the production of IL-6 by stimulated macrophages. The effect was not dependent on its well-known anti-endotoxin activity since TRD inhibited cytokine production by macrophages stimulated with either LPS or IFN-gamma. Finally, we report that anti-inflammatory activities of TRD and taurine haloamines are mediated by different mechanisms. TRD, in contrast to TauCl and TauBr, does not induce expression of HO-1, a stress inducible enzyme with strong anti-inflammatory properties.

Animals↗
PubMed2005

Leukotrienes modulate cytokine release from dendritic cells.

Leukotriene B(4) (LTB(4)) and cysteinyl leukotrienes (CysLTs) are known as potent mediators of inflammation, whereas their role in the regulation of adaptive immunity remains poorly characterized. Dendritic cells (DCs) are specialized antigen-presenting cells, uniquely capable to initiate primary immune responses. We have found that zymosan, but not lipopolysaccharide (LPS) stimulates murine bone marrow-derived dendritic cells (BM-DCs) to produce large amounts of CysLTs and LTB(4) from endogenous substrates. A selective inhibitor of leukotriene synthesis MK886 as well as an antagonist of the high affinity LTB(4) receptor (BLT(1)) U-75302 slightly inhibited zymosan-, but not LPS-stimulated interleukin (IL)-10 release from BM-DCs. In contrast, U-75302 increased zymosan-stimulated release of IL-12 p40 by approximately 23%. Pre-treatment with transforming growth factor-beta1 enhanced both stimulated leukotriene synthesis and the inhibitory effect of U-75302 and MK886 on IL-10 release from DCs. Consistent with the effects of leukotriene antagonists, exogenous LTB(4) enhanced LPS-stimulated IL-10 release by approximately 39% and inhibited IL-12 p40 release by approximately 22%. Both effects were mediated by the BLT(1) receptor. Ligands of the high affinity CysLTs receptor (CysLT(1)), MK-571 and LTD(4) had little or no effect on cytokine release. Agonists of the nuclear LTB(4) receptor peroxisome proliferator-activated receptor-alpha, 8(S)-hydroxyeicosatetraenoic acid and 5,8,11,14-eicosatetraynoic acid, inhibited release of both IL-12 p40 and IL-10. Our results indicate that both autocrine and paracrine leukotrienes may modulate cytokine release from DCs, in a manner that is consistent with previously reported T helper 2-polarizing effects of leukotrienes.

Animals↗
PubMed2004

Dynamics of selected MHC class I and II molecule expression in the course of HPV positive CIN treatment with the use of human recombinant IFN-gamma.

BACKGROUND: Studies consistently reveal downregulation of major histocompatibility complex (MHC)-I molecules or/and selective loss of individual MHC-I alleles and upregulation of MHC-II molecules in the areas of cervical intraepithelial neoplasia (CIN) and in cervical cancers. In vitro studies demonstrated the interferon-gamma (IFN-gamma) potential of MHC class I and II molecule upregulation followed by increased cytolytic response against some cervical cancer cell lines. AIM OF THE STUDY: In vivo assessment of the correlation between regression/persistence state of CIN and the IFN-gamma-induced changes in both class of selected MHC molecule expression. METHODS: Seventeen subjects with CIN I/CIN II associated with high-risk HPV infection underwent uniform IFN-gamma treatment (four intracervical injections over 2-day interval for a total dose of 6,000,000 IU). Immunohistochemical staining has been performed within cervical punch biopsy specimens with the use of monoclonal antibody reacting with HLA-DR, HLA-HC and HLA-Bw4, and the mean proportion of given molecules expressing keratinocytes was counted before, immediately after and 2 months after IFN-gamma treatment RESULTS: The analysis revealed a rapid and significant increase of the HLA-Bw4 proportion in response to IFN-gamma, persistent in the group of complete responders (with CIN clearance). No significant changes in the proportion of HLA-HC 10 positive cells in response to IFN-gamma administration was demonstrated, nor a significant increase in HLA-DR positivity; however, the transient trend towards increasing the proportion of HLA-DR immediately after treatment completion was observed. CONCLUSIONS: Upregulation of selected MHC class I allele expression, but not necessary MHC class II or heavy chain fragments of MHC-I, induced by IFN-gamma correlates with the resolution of cervical intraepithelial lesions and high-risk HPV DNA clearance in vivo.

Adult↗
PubMed2004

[Characteristics of the Propionibacterium strains isolated from acne patients].

Propionibacterium acnes is a component of physiological flora of human skin. It colonizes the outlets of sebaceous glands and participates in the pathogenesis of inflammatory acne. Acne vulgaris is a common skin disease. It is found in more or less exacerbated form in approximately 85% of adolescent population. The main purpose of the research was to confirm the hypothesis of Propionibacterium bacteria participation in the aetiopathogenesis of acne vulgaris. The researches have proved the presence of Propionibacterium acnes on the surface of the skin both of people with acne-related changes and these with whom such changes were not found. Statistically significant differences were found in the number of P. acnes bacteria per 1 square centimeter of healthy and disease-affected skin as well as in the diversity of biochemical types. The highest number of P. acnes bacteria have been found in fresh changes with visible symptoms of inflammation. In order to confirm the hypothesis of the participation of Propionibacterium bacteria in the aetiopathogenesis of acne, a detailed phenotypical analysis of isolated P. acnes strains have been conducted. Type, biotype, resistance pattern, proteolytic and lipolytic properties have been determined.

Acne Vulgaris↗
PubMed2003

Prostanoids and MPO-halide system products as a link between innate and adaptive immunity.

and The crosstalk between innate adaptive immunity is regulated by cytokines and complex interactions between cells of the immune system. A variety of endogenous agents are involved in the regulation of the cytokine network. Especially, eicosanoids and ROIs have a great impact on the regulation of cytokine production. Eicosanoids (prostanoids, leukotrienes and lipoxins) are produced mainly by inflammatory cells while their receptors are distributed on the cells of both arms of the immune system. Depending on the predominant prostanoid produced and the profile of prostanoid receptors expression on immune cells, eicosanoids can selectively regulate the production of Th1 and Th2 driven cytokines. Inflammatory cells (neutrophils, macrophages), are also a rich source of large amounts of ROIs. In this paper we have focused on the role of taurine chloramine (TauCl), the physiological product of neutrophil MPO-halide system, in the regulation of immune system. It is well documented that TauCl has pleiotropic effects on the inductive phase of the immune response. TauCl's immunoregulatory properties result from its ability to modulate the production of cytokines and eicosanoids. Finally, we conclude that eicosanoids and ROIs provide an important link between the afferent branches and the innate and adaptive immune response.

Animals↗
PubMed2003

Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine.

OBJECTIVE: To investigate the effects of taurine chloramine (Tau-Cl), a chlorinated derivative of the amino acid taurine, on the expression of cyclooxygenase (COX) isoenzymes and prostaglandin E(2) (PGE(2)) synthesis in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). METHODS: FLS, isolated from the synovial tissue of RA patients, were treated in vitro with either interleukin-1beta (IL-1beta; 1 ng/ml) alone or together with 200-500 microM Tau-Cl. The expression of COX isoenzymes was evaluated at both the protein (Western blotting) and the messenger RNA (mRNA) (reverse transcriptase-polymerase chain reaction) levels. The concentration of PGE(2) was measured by competitive acetylcholinesterase enzyme immunoassay. RESULTS: Resting FLS expressed mRNA encoding both COX-1 and COX-2, but only COX-1 was present at the protein level. These cells produced negligible amounts of PGE(2). Upon stimulation with IL-1beta, elevation of COX-2, but not COX-1, mRNA and protein preceded the enhancement of PGE(2) synthesis. In the presence of 300-400 microM Tau-Cl, significant inhibition of IL-1beta-triggered COX-2 mRNA and protein, and a related decrease in PGE(2) production, was observed. In contrast, no significant changes in COX-1 mRNA and protein levels were noted. CONCLUSION: Tau-Cl inhibits IL-1beta-triggered elevation of COX-2 and generation of PGE(2) by RA FLS. These results expand the spectrum of known antiinflammatory activities of this compound.

Arthritis, Rheumatoid↗
PubMed2003

Exogenous but not endogenous prostanoids regulate cytokine secretion from murine bone marrow dendritic cells: EP2, DP, and IP but not EP1, EP3, and FP prostanoid receptors are involved.

Murine bone marrow-derived dendritic cells (DC), stimulated with lipopolysaccharide (LPS) and/or LPS+interferon-gamma (IFN-gamma), secrete a variety of inflammatory mediators which may modulate their functions. We have examined the potential for exogenous prostanoids, acting in a paracrine fashion, and endogenous prostanoids, acting in an autocrine fashion, to regulate secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, and IL-12 in DC. In order to identify receptors mediating these effects, DC were treated in vitro with receptor-selective prostanoids. Agonists of cyclic AMP-elevating receptors, namely, prostaglandin E(2) (PGE(2)), butaprost (EP(2) receptor), iloprost (IP receptor), and BW245C (DP receptor), dose-dependently inhibited the release of IL-6, TNF-alpha, and IL-12 and enhanced the release of IL-10 from LPS-stimulated DC, with TNF-alpha secretion being the most strongly affected. In contrast, 15-deoxy-Delta(12,14)-PGJ(2)-an activator of nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptors-inhibited release of all tested cytokines. Exogenous prostanoids, cyclic AMP-elevating analogs, lost their ability to modulate cytokine release in cells pre-incubated for 4 h with LPS, indicating that prostanoids may affect DC functions during initial phases of LPS stimulation only. Sulprostone and (+)-fluprostenol failed to modulate any of responses tested, suggesting lack of involvement/expression of EP(1), EP(3), and FP receptors in DC activation. In order to examine the role of endogenous prostanoids, DC were treated with inhibitors of cyclooxygenases (COX). At concentrations that completely blocked PGE(2) release, neither indomethacin (nonselective inhibitor) nor rofecoxib (COX-2-selective inhibitor) influenced cytokine release from LPS-stimulated DC. Thus, cytokine release from LPS-stimulated DC does not seem to be autoregulated by endogenous prostanoids, whereas in vivo regulatory function may be fulfilled in a paracrine manner by PGD(2), PGE(2), and PGI(2) released from neighboring cells.

Animals↗
PubMed2003

Alterations in the expression of selected MHC antigens in premalignant lesions and squamous carcinomas of the uterine cervix.

BACKGROUND: The objective of the study was to determine whether there is a correlation between expression of selected major histocompatibility complex (MHC) antigens and the presence of carcinoma and premalignant lesions of the cervix. We also attempted to determine whether there is a correlation between expression of the selected MHC antigens in each grade of cervical intraepithelial neoplasia (CIN) and invasive carcinoma of the cervix. METHODS: Quantitative comparative analysis of MHC class I and class II expression between specimens of the uterine cervix was carried out. For detecting human leukocyte antigen (HLA) class I molecules, two primary antibodies were used, recognizing either epitopes of all free heavy chain class I molecules or epitopes of the HLA-Bw4 antigen. HLA class II antigens were detected by antibodies reacting with the alpha-chain of the HLA-DR molecule. An indirect immunoperoxidase technique was carried out using paraffin-embedded sections. The following groups of sections were formed: squamous metaplasia, CIN of different grades, and invasive carcinoma. The specimens were taken from women in whom routine histopathologic diagnosis of cervical lesions had been performed. RESULTS: A significant decrease in the mean number of stained cells showing expression of MHC class I antigens (HC 10 and Bw4) was found in the invasive cancer group of specimens. A decrease in Bw4 expression was also found in the CIN III group. The highest expression of the HLA-DR antigens was detected in the metaplastic epithelium compared to the other groups. In the dysplastic epithelium the expression of the HLA-DR antigens was increased in the highest grade of dysplasia (CIN III). Upregulation of HLA-DR expression was detected in invasive cancer specimens. CONCLUSIONS: Alterations in MHC expression are found in premalignant lesions and squamous carcinomas of the uterine cervix. Quantitative assessment with the use of an image analysis system is valuable in helping to discriminate staining patterns of HLA expression. Further studies are indicated to evaluate the prognostic value of the expression of selected MHC antigens.

Biomarkers, Tumor↗
PubMed2003

Collagen type II modification by hypochlorite.

Oxidation of proteins is a common phenomenon in the inflammatory process mediated by highly reactive agents such as hypochlorite (HOCl/OCl(-)) produced by activated neutrophils. For instance, in rheumatoid arthritis hypochlorite plays an important role in joint destruction. One of the major targets for HOCl/OCl(-) is collagen type II (CII) - the primary cartilage protein. In our study, HOCl/OCl(-) mediated collagen II modifications were tested using various methods: circular dichroism (CD), HPLC, ELISA, dynamic light scattering (DLS), fluorimetry and spectrophotometry. It was shown that hypochlorite action causes deamination with consecutive carbonyl group formation and transformation of tyrosine residues to dichlorotyrosine. Moreover, it was shown that ammonium chloramine (NH(2)Cl) formed in the reaction mixture reacts with CII. However, in this case the yield of carbonyl groups and dichlorotyrosine is lower than that observed for HOCl/OCl(-) by 50%. CD data revealed that collagen II exists as a random coil in the samples and that chlorination is followed by CII fragmentation. In the range of low HOCl/OCl(-) concentrations (up to 1 mM) 10-90 kDa peptides are predominant whereas massive production of shorter peptides was observed for high (5 mM) hypochlorite concentration. DLS measurements showed that chlorination with HOCl/OCl(-) decreases the radius of collagen II aggregates from 30 to 6.8 nm. Taking into account the fact that chlorinated collagen is partially degraded, the DLS results suggest that smaller micelles are formed of the 10-90 kDa peptide fraction. Moreover, collagen chlorination results in epitope modification which affects CII recognition by anti-CII antibodies. Finally, since in the synovial fluid the plausible hypochlorite concentration is smaller than that used in the model the change of size of molecular aggregates seems to be the best marker of hypochlorite-mediated collagen oxidation.

Amino Acids↗
PubMed2002

Myeloperoxidase-mediated protein oxidation: its possible biological functions.

Oxidation of proteins occurs both as a side-effect of aerobic energy metabolism and as an effect of specific metabolism of phagocytic polymorphonuclear granulocytes producing O2- and H2O2. In contrast to other cells, which control their H2O2 level by degrading it to O2 and H2O, polymorphonuclear neutrophilic leukocytes (PMN) use H2O2 as a substrate for oxidizing chloride ions to HOCl which rapidly react with all neighboring thiol, disulfide and amino residues. Chloramines, which are the most abundant HOCl reaction products, react with proteins, modifying only certain exposed methionine and cysteine residues. This may account for selective inactivation of a number of enzymes, carrier proteins and peptide mediators, including the alpha1-proteinase inhibitor, alpha2-macroglobulin and plasminogen activator inhibitor. Inactivaton of plasma proteinase inhibitors protects PMN elastase, collagenase, cathepsin G and other serine proteases in the inflammatory foci. This promotes proteolytic degradation of damaged tissue, removal of bacterial debris and wound healing, as well as tissue remodeling related to the inflammatory processes. Oxidative control of protease-anti-protease balance affects the development of the inflammatory processes. Moreover, inactivation of plasma proteinase inhibitors facilitates primary antigen processing, upregulates lymphocyte proliferative response and activates the local immune response. Oxidation produces a specific protein tagging which attracts and stimulates immune active cells. Therefore, humoral response against oxidatively modified proteins occurs more effectively than that of the native proteins. The effect is dose-dependent with respect to the amount of oxidant employed. Glycol aldehyde, which is the serine chloramine spontaneous decay product, in mice immunized with glycol aldehyde-modified egg-white albumin, yields specific IgG production manifold higher than that in mice immunized with native albumin. Immunopotentiation is produced by proliferation expansion of the same immunocompetent clones. Oxidative tagging of proteins may also affect the autoimmune-type reaction. Thus, a growing body of data suggest that the specific role of protein oxidation by activated PMN is oxidative protein tagging facilitating further development of the immune reaction.

Animals↗
PubMedDate not supplied

Oxidative modification of type II collagen differentially affects its arthritogenic and tolerogenic capacity in experimental arthritis.

INTRODUCTION: Oxidative modification of proteins affects their biological properties. Previously we have shown that hypochlorite (HOCl), the product of activated neutrophils, enhances protein immunogenecity. Collagen type II, a primary component of cartilage, is commonly used in the induction of arthritis in animals (CIA). The aim of this study was to examine whether HOCl may affect immunogenic, tolerogenic, and arthritogenic properties of collagen. MATERIALS AND METHODS: DBA/J mice were injected with either native (CNAT) or chlorinated collagen (CHOCl) to induce arthritis. The effect of chlorination on collagen properties was measured by evaluation of incidence and severity of CIA. Moreover, the concentration of serum anti-collagen IgG antibodies and myeloperoxidase (MPO) activity in inflamed joints was determined. RESULTS: Mice immunized with CNAT in adjuvant developed arthritis (CIA) with an incidence of 69%. CNAT also exerted tolerogenic properties when injected intravenously either before or shortly after primary immunization, resulting in decreased incidence and severity of CIA, reduced MPO activity in inflamed joints, and lowered serum levels of anti-CNAT IgG anti-bodies. Chlorination of collagen significantly diminished its ability to induce CIA and to trigger generation of anti-CNAT IgG antibodies. Interestingly, chlorination did not affect tolerogenic properties of collagen administered prior to primary immunization with CNAT. CONCLUSIONS: These results suggest that chlorination of collagen may selectively affect functional epitopes of collagen. It is likely that in inflamed joints, neutrophil derived HOCl, in some circumstances, will destroy arthritogenic and immunogenic B cell epitopes, while regulatory T cell epitopes will be preserved.

Animals↗
PubMedDate not supplied

Different pro-inflammatory and immunogenic potentials of Propionibacterium acnes and Staphylococcus epidermidis: implications for chronic inflammatory acne.

INTRODUCTION: Propionibacterium acnes (PA) and Staphyloccocus epidermidis (SE) are two major bacterial strains isolated from acne lesions. Nevertheless, only PA seems to be implicated in the pathogenesis of inflammatory acne vulgaris. Evidence for this, however, remains indirect and the precise role of PA in inflammatory acne is still a matter for conjecture. The aim of this study was to compare some pro-inflammatory and adjuvant properties of PA and SE. MATERIAL/METHODS: To determine some of the pathogenic, immunostimulatory, and pro-inflammatory proper of PA and SE, two experimental models of inflammation were used. In vivo; chronic inflammation was induced by intradermal injection of living bacteria into the ear. In vitro; peritoneal macrophages elicited by the bacteria were examined for their ability to generate reactive oxygen species (ROS), nitric oxide (NO), and cytokines. RESULTS: PA, but not SE, evoked mild local inflammation of infected ears. Macrophages elicited with PA produced more tumor necrosis factor alpha and interleukin IL-12 than those induced with SE, while SE was a stronger inducer of IL-10 production. Both bacteria equally induced the generation of NO and ROS. In contrast, only PA showed adjuvant proper-ties. CONCLUSIONS: The results of these studies indicate that SE, in contrast to PA, does not exert pro-inflammatory properties. Thus it is unlikely that SE may be implicated in the pathogenesis of inflammatory acne vulgaris.

Acne Vulgaris↗