Objectives of the study were to investigate impact of ischemic preconditioning (Ipre) and sulforaphane (SFN) and combination of them on nuclear factor 2 erythroid related factor 2 (Nrf2) gene and its dependent genes, heme oxygenase-1 (HO1) and NADPHquinone oxidoreductase1 (NQO-1) and inflammatory cytokines TNF-α, IL1β, and intercellular adhesion molecule-1 (ICAM1) and caspase-3 in renal ischemia/reperfusion (I/R) injury. Ninety male Sprague Dawely rats were classified into 5 groups (each consists of 18 rats): sham, control, Ipre, sulforaphane and Sulfo+Ipre. Each group was subdivided into 3 subgroups each containing 6 rats according to time of harvesting kidney and taking blood samples; 24 h, 48 h, and 7 days subgroups. Renal functions including serum creatinine, BUN were measured at basal conditions and by the end of experiment. Expression of Nrf2, HO-1, NQO-1, TNF-α, IL-1β, and ICAM-1 was measured by real time PCR in kidney tissues by the end of experiment. Also, immunohistochemical localization of caspase-3 and chemical assay of malondialdehyde (MDA), GSH and SOD activity were measured in kidney tissues. Both Ipre and SFN improved kidney functions, enhanced the expression of Nrf2, HO-1, and NQO-1, attenuated the expression of inflammatory (TNF-α, IL-1, and ICAM-1) and apoptotic (caspase-3) markers. However, the effect of sulforaphane was more powerful than Ipre. Also, a combination of them caused more improvement in antioxidant genes expression and more attenuation in inflammatory genes but not caspase-3 than each one did separately. Sulforaphane showed more powerful effect in renoprotection against I/R injury than Ipre as well as there might be a synergism between them at the molecular but not at the function level., A. A. Shokeir, N. Barakat, A. M. Hussein, A. Awadalla, A. M. Harraz, S. Khater, K. Hemmaid, A. I. Kamal., and Obsahuje bibliografii
Tumour necrosis factor (TNF) plays a central role in the inflammatory process. In the skin, it contributes to immune containment of tick-transmitted pathogens like Borrelia burgdorferi. In the saliva of some tick species, active compounds are present that inhibit detection of TNF in specific ELISA. We compared the presence of anti-TNF activity in saliva or salivary gland extract from 11 tick species from the family Ixodidae and demonstrated it in genera Ixodes Latreille, 1795 and Haemaphysalis Koch, 1844. Analysis of anti-TNF activity in Ixodes ricinus (Linnaeus, 1758) saliva during the feeding period showed that it is present in the late, rapid phase of engorgement. Significance of anti-TNF activity for tick feeding and transmission of tick-borne pathogens is discussed., Markéta Rezková, Jan Kopecký., and Obsahuje bibliografii
Autoimmune endocrinopathies can be divided according to the presence of organ specific autoantibodies and according to the clinical manifestations into isolated autoimmune endocrinopathies, autoimmune polyglandular syndromes (APS) and polyglandular activation of autoimmunity (PAA). Many factors take part in the development of the autoimmune disease: predominantly a genetic predisposition, environmental etiologic causes and dysregulation in the microenvironment of the target organ. Until now it is not completely clear, if manifestations of the clinical disease depend primarily upon external factors and the degree of regulation mechanism disorder (e.g. in Th1/Th2 regulation) or upon the different genetic predisposition. In this work we compared the levels of Th1 and Th2 lymphocyte cytokines in peripheral blood in three groups of patients: group A of 30 patients with autoimmune thyroiditis, group B of 25 patients with PAA, and group C of 10 patients with APS type II. From group of Th1 cytokines IL-2 and IFN-Ύ were detected, whereas from group of Th2 cytokines IL-4 and IL-10 were determined by ELISA kit. We did not find any differences in the concentrations of IL-2, IFN-Ύ, IL-4 and IL-10 among the groups of patients with autoimmune endocrinopathies., P. Hrdá, I. Šterzl, P. Matucha., and Obsahuje bibliografii
The production of three cytokines, interferon gamma (IFN-y), interleukin 10 (1L-10) and interleukin 12 (IL-12), was measured after intraperitoneal infection of immunocompetent Balb/c mice and immunodeficient SCID mice with the microsporidian, Encephalitozoon cuniculi Levaditi, Nicolau ct Schoen, 1923. High levels of IFN-y were detected in ex vivo cultures of peritoneal exudate cells (PEC) of Balb/c mice, a lower, but earlier IFN-y response was observed in PEC from SCID mice. The early 1L-10 response was detected in ex vivo cultures of splenocytes from Balb/c but not from SCID mice, explaining a delay in the IFN-y response in Balb/c mice. IL-12 was detected in PEC cultures from SCID mice, indicating an alternative pathway of IFN-y production by NK. cells stimulated by IL-12 derived from macrophages.
Cytokiny jsou proteiny, které regulují růst, diferenciaci a aktivaci buněk. Jejich účinek se široce využívá pro léčbu zánětlivých a nádorových onemocnění. Anti-cytokinová léčba je velmi slibná, ale přinese v blízké budoucnosti velké finanční zatížení zdravotnictví., Cytokines are proteins that regulate the growth, differentiation and activation of cells. Their functions are used in therapy of inflammatory diseases and cancer. Antibody blockade of cytokines seems to be very promising, but it will result in considerable financial burden for healthcare in future., and Ilja Trebichavský.
To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-a, IL-10 and finally also IL-1b. Productions of IL-12 and INF-g are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1b and TNF-a significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-g were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-g, besides IL-1b, TNF-a, IL-6 and IL-10. Productions of IL-1b, IL-6 and TNFa increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-g begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines., L. Janský, P. Reymanová, J. Kopecký., and Obsahuje bibliografii
To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-a, IL-10 and finally also IL-1b. Productions of IL-12 and INF-g are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1b and TNF-a significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-g were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-g, besides IL-1b, TNF-a, IL-6 and IL-10. Productions of IL-1b, IL-6 and TNFa increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-g begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines., L. Janský, P. Reymanová, J. Kopecký., and Obsahuje bibliografii
Previous studies have demonstrated that both tick saliva and Borrelia burgdorferi sensu lato antigens modulate the cytokine response of the host. In this paper, the effect of salivary gland extract (SGE) from Ixodes ricinus (L., 1758) ticks on cytokine production by primary cultures of mouse epidermal cells stimulated with Borrelia afzelii Canica, Nato, du Merle, Mazie, Baranton et Postic, 1993 spirochetes was analysed. Epidermal cells were derived from C3H/HeN mice, susceptible to Lyme disease, and BALB/c mice, which are resistant. In cultures from C3H/HeN mice, SGE down regulated production of tumour necrosis factor alpha (TNF-α) and up regulated Th2 cytokine, interleukin 4 (IL-4). Cultures from BALB/c mice produced higher basal levels of monitored cytokines, but their production was affected by SGE a different way. While Th2 cytokines IL-6 and IL-10 were down regulated, the effect on TNF-α and IL-4 was ambiguous. These results indicate that the effect of tick saliva on the epidermal cells of Lyme disease-susceptible C3H/HeN mice mirrors its effect on other cells of the immune system.
There is an increasing eviden ce linking dysbalance between various proinflammatory mediators and higher risk of cardiovascular events and pathologies. Likewise, some of the cardiovascular diseases lately ap peared to have an autoimmune component. Interleukin-1 (IL-1), a master regulator of diverse inflammatory processes in higher eukaryotes and the key player in numerous autoimmune disorders including rheumatoid arthritis, diabetes mellitus or systemic sclerosis, has recently been proved to be involved in development of several cardiovascular diseases as well. This report aims to give a summary on current knowledge about the IL-1 signaling pathways and about the implication of IL-1 and the IL-1 receptor antagonist (IL-1Ra) in some of the diseases of the cardiovascular system., B. Vicenová ... [et al.]., and Obsahuje seznam literatury
As environmental and genetic components contribute to the PCOS expression, we compared levels of endocrine disruptors, steroid hormones, cytokines, and metabolic parameters in twenty healthy, nine normal-weight PCOS women, and ten obese PCOS women. Steroid hormones, bisphenols (BPA, BPS, BPF, BPAF) and parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-parabens) were measured by liquid chromatography-tandem mass spectrometry. Differences between the groups were assessed using the Mann-Whitney U test. Spearman correlation coefficients were calculated for the individual parameters relationship. Significantly higher levels of BPA, anti-Müllerain hormone, lutropine, lutropine/folitropine ratio, testosterone, androstenedione, 7β-OH-epiandrosterone, and cytokines (IL-6, VEGF, PDGF-bb), were found in normal-weight PCOS women compared to controls. Between normal-weight and obese PCOS women, there were no differences in hormonal, but in metabolic parameters. Obese PCOS women had significantly higher insulin resistance, fattyliver index, triglycerides, cytokines (IL-2, IL-13, IFN-γ). In healthy, but not in PCOS, women, there was a positive correlation of BPA with testosterone, SHBG with lutropine, and folitropine, while testosterone negatively correlated with SHBG. In obese women with PCOS, insulin resistance negatively correlated with SHBG and estradiol. No differences were observed in the paraben exposure. Levels of BPA were higher in PCOS women, indicating its role in the etiology. Obesity significantly worsens the symptoms., Markéta Šimková, Jana Vítků, Lucie Kolátorová, Jana Vrbíková, Michala Vosátková, Josef Včelák, Michaela Dušková., and Obsahuje bibliografii