[Determination of antispermal IgE antibodies in women with infertility and chronic inflammatory pelvic diseases.] / Определение Ð°Ð½Ñ‚Ð¸ÑÐ¿ÐµÑ€Ð¼Ð°Ð»ÑŒÐ½Ñ‹Ñ IgE антител у женщин с бесплодием, ÑÑ‚Ñ€Ð°Ð´Ð°ÑŽÑ‰Ð¸Ñ Ñ Ñ€Ð¾Ð½Ð¸Ñ‡ÐµÑÐºÐ¸Ð¼Ð¸ воспалительными заболеваниями органов малого таза.

Personalized therapy for female infertility means determining of immune mechanisms, including allergic sensitization towards sperm antigens. In order to determine antisperm serum IgE antibodies in women with infertility suffering from pelvic inflammatory diseases, the modified Anti-Spermatozoa Antibody protocol was used (ASA Serum ELISA, Demeditec Diagnostisc, Germany). The modification of the protocol is designed to detect only serum antisperm IgE antibodies carrying Fab fragments to sperm antigens. Allergen-specific IgEs to a common panel of 176 respiratory and food allergenic molecules were determined using the MeDALL scientific chip developed as a part of the European project. Forty patients suffering from infertility of inflammatory etiology and 16 practically healthy women of reproductive age were examined. Specific IgE antibodies towards sperm antigens were detected in blood serum in 7/40 (17.5%) patients with infertility. The maximum level of sIgE was 4 times higher than the maximal value of fertile women. No correlation with total IgE was detected. Women with sIgE-ASA complained of burning and itching immediately after coition. Systemic and long-term allergic reactions were not noted. Women with positive sIgE-ASA values were 2 times more likely to suffer from chronic recurrent vaginal dysbiosis. The presence of specific anti-sperm IgE antibodies is likely to have pathogenetic significance in female infertility, and they should be taken into consideration for creating personalized therapy approaches.

Possible effect of landscape design on IgE recognition profiles of two generations revealed with micro-arrayed allergens.

The aim of this study was to investigate possible effects of landscape design on the IgE sensitization profile toward inhalant allergens in patients with respiratory allergy from Uzbekistan where green areas have been changed during the last two decades by a State program. Sera from two different generations of Uzbek (n=58) and, for control purposes, from two generations of Austrian (n=58) patients were analyzed for IgE reactivity to 112 different micro-arrayed allergen molecules by ImmunoCAP ISAC technology. Changes in molecular IgE sensitization profiles to pollen allergens in the young vs the middle-aged Uzbek population were associated with replanting, whereas those in the Vienna populations reflected natural changes in plant growth. Our data indicate that anthropologic as well as natural changes in the biome may have effects on IgE sensitization profiles already from one to another generation.

Inactivation of Inflammasomes by Pathogens Regulates Inflammation.

Inflammatory response is initiated and sustained by the action of quintessential pro-inflammatory cytokines of immune system namely IL-1ß and IL-18. The maturation process of those cytokines is ensured by caspase-1 enzymatic activity, that is in turn is tightly controlled by multiprotein complexes called inflammasomes. Inflammasomes are activated in cells of innate immune system in response to recognition of conservative parts of microbes (pathogen-associated molecular patterns) or by sensing molecular signs of tissue damage (damage-associated molecular patterns). Inflammasome activation apart of cytokines secretion leads to pro-inflammatory cell death, so-called pyroptosis. That culminates in release of cytoplasmatic content of cells including cytokines and alarmins that boost immune response against pathogens, as well as pyroptosis destroys replicative niches of intracellular pathogens. During co-evolution with the host, bacterial and viral pathogens developed a range of molecular inhibitors targeting each step of inflammasome activation. In current review, we will discuss the latest knowledge of inflammasomes' signaling pathways and tricks that pathogens use to avoid immune recognition and clearance. Our better understanding of inflammasome inhibition by pathogens can lead to better therapeutic approaches for the treatment of infectious diseases.

Propofol-induced calcium signalling and actin reorganization within breast carcinoma cells.

BACKGROUND AND OBJECTIVE: MDA-MB-468 breast carcinoma cells respond to non-volatile anaesthetics such as propofol with an increased migration. Here we investigated the relationship between GABA-A receptor modulators, the mode of calcium oscillation and actin reorganization with regard to breast carcinoma cell migration. METHODS: Expression of the GABA-A receptor was determined by Western blot analysis. Calcium-imaging experiments of individual MDA-MB-468 cells as well as visualization of the F-actin distribution were performed by confocal laser scanning microscopy. Cell migration was investigated in a three-dimensional collagen matrix by time-lapse video microscopy. The GABA agonist propofol was used in a final concentration of 6 microg mL(-1). GABA-A receptor antagonist bicuculline (50 micromol) and selective L-type calcium channel blocker verapamil (5 micromol) were used to modulate the propofol effects. RESULTS: A functional GABA-A receptor is expressed by MDA-MB-468 cells. Activation with propofol resulted in sustained increased intracellular calcium concentrations concomitant with actin reorganization and induction of migration in MDA-MB-468 cells. These propofol effects were completely blocked by verapamil. Spontaneous migration of MDA-MB-468 cells (64.4 +/- 7.0%) was significantly increased by propofol to 85.0 +/- 5.0%. MDA-MB-468 cells co-treated with propofol and verapamil showed a migratory activity of 63.0 +/- 2.0% indicating that verapamil blocked the propofol effect. Similar results were achieved with the GABA-A receptor inhibitor bicuculline (control: 56.3 +/- 8.5%; propofol: 80.5 +/- 7.1%; propofol + bicuculline: 52.5 +/- 8.6%). CONCLUSION: Activation of GABA-A receptor by propofol correlated with an increased migration of MDA-MB-468 breast carcinoma cells, mediated by calcium influx via L-type calcium channels and reorganization of the actin cytoskeleton.

Influence of non-volatile anesthetics on the migration behavior of the human breast cancer cell line MDA-MB-468.

BACKGROUND: Anesthetic agents are known to influence functions of the immune system. Anesthetic drugs also support cancer progression by suppressing the activity of immune cells. In breast carcinoma an increase in expression of peripheral-type benzodiazepine receptors (PBR) and the gamma aminobutyl acid (GABA) level has been discovered. Therefore, an investigation of a direct influence of GABA-A agonist propofol, GABA-A and PBR-agonist etomidate, and the local anesthetic drug lidocaine, which can also bind to the GABA-A receptor and PBR, on migration of breast carcinoma cells was performed. METHODS: MDA-MB-468 cells were incubated with anesthetic agents using clinically relevant concentrations (propofol 3, 6, 9 mg/l, etomidate 2, 3, 4 mg/l, and lidocaine 1.25, 2.5, 5 mg/l). Locomotion was investigated in a three-dimensional collagen matrix using time-lapse video microscopy and computer-assisted cell-tracking. RESULTS: The percentage of migrating cells (57.4+/-1.9) as well as the velocity (0.22+/-0.09 microm/min) and distance migrated (89.4+/-66.8 microm/10 h) increased in the presence of propofol in a dose-dependent manner (up to 74.4+/-7.5, 0.30+/-0.09, 143.8+/-89.1, respectively) compared with the long chain triglyceride (LCT) control. In contrast, no influence of etomidate on the number of migrating cells could be observed. The velocity and distance migrated at 3 and 4 mg/l were found to be statistically significantly enhanced. Treatment with lidocaine caused an increase in the percentage of migrating cells (up to 75.0+/-5.6) in velocity dose dependently (up to 0.33+/-0.06) and in distance migrated (up to 151.5+/-92.9). CONCLUSION: These results show that different anesthetic drugs are able to modulate the migratory machinery of human breast carcinoma cells in vitro.