Barbara Kur

Expression of Th1/Th2/Th3/Th17-Related Genes in Recurrent Aphthous Ulcers

The pathogenesis of recurrent aphthous ulceration (RAU) is unknown, although an abnormal immune reaction appears to be involved. RAU may result from oral epithelium damage caused by T cell-mediated immune response. To improve understanding of the role of T cells in RAU, the present study analyzed. the expression of T cell-related genes in oral ulcers from patients with RAU, as well as in healthy non-keratinized oral mucosa from aphthae-free volunteers. Biopsies from RAU patients and healthy individuals were analyzed using Human Th1-Th2-Th3 RT2 Profiler PCR Array and qRT-PCR that allowed to quantify the transcript levels of 86 genes related to T cell activation. We found that cells present in aphthous ulcers express a characteristic Th1-like gene profile. The majority of genes up-regulated in aphthous lesions such as IFN-γ, TNF, IL-15, IRF1, STAT-1 and STAT-4 were Th1-associated. Th2-realated genes were not overexpressed in RAU tissues, with the exception for CCR3. Th3- and Th17-related gene expression patterns were not demonstrated in RAU. These findings clearly reveal that aphthous ulcer formation is predominantly dependent on the activation of the Th1-type immune response.

The inflammatory response in lungs of rats exposed on the airborne particles collected during different seasons in four European cities

Epidemiological studies have reported associations of ambient particulate air pollution, especially particulate matter (PM) less than 10 μm with exacerbations of asthma and chronic obstructive pulmonary disease. In an in vivo model, we have tested the toxicity of urban airborne particles collected during spring, summer, and winter seasons in four cities (Amsterdam, Lodz, Oslo, and Rome) spread across Europe. The seasonal differences in inflammatory responses were striking, and almost all the study parameters were affected by PM. Coarse fractions of the urban particle samples were less potent per unit mass than the fine fractions in increasing cytokine [macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)-α] levels and in reducing Clara-cell secretory protein (CC16) levels. This study shows that PM collected at 4 contrasting sites across Europe and during different seasons have differences in toxic potency. These differences were even more prominent between the fine and coarse fractions of the PM.

Perinatal exposure of mice to TCDD decreases allergic sensitisation through inhibition of IL-4 production rather than T regulatory cell-mediated suppression.

OBJECTIVE The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread, man-made, persistent organic pollutant with high immunotoxic potentials. It suppresses cell-mediated and humoral immune responses through mechanisms dependent on aryl-hydrocarbon receptor expression and immunosuppressive activity of the cells. Most sensitive to TCDD are organisms during fetal and infant life, mostly due to the developmental stage of many biological systems of the host, including immune system. Recent data show that T regulatory cells that have the potential to suppress immune reactions and which develop after TCDD exposure are also responsible for protection from allergy development. Our goal was to investigate if perinatal exposure to TCDD can affect allergic sensitisation and if T reg cells participate in this phenomenon. MATERIALS AND METHODS Mice, Balb/c, were perinatally exposed to TCDD or to the carrier. Six weeks old control or exposed mice were sensitised with ovalbumin. Spleen cells of the animals were used to assess the content of T reg cells by means of flow cytometry. Levels of cytokines were assessed by ELISA technique in supernatants of the cells stimulated with anti-CD3 antibody. As a measure of sensitisation, total IgE and anti-OVA IgE were measured in serum of mice by ELISA method. To assess the function of T reg cells isolated from OVA-sensitised control or TCDD exposed animals we performed transfer studies. RESULTS Here we show that perinatal exposure to TCDD decreases allergic sensitisation and that this process is related to inhibition of IL-4 synthesis rather than suppression mediated by T regulatory cells. CONCLUSION We hypothesise that dioxin exposure can be an important environmental modulator of immunological responses that participate in allergic reactions.

Pulmonary Irritation After Inhalation Exposure to Benzalkonium Chloride in Rats

BACKGROUND Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) with a C8 to C18 chain length of alkyl groups. Since BAC exerts toxic effects on microorganisms, it has been used as an effective germicide and preservative, mostly in cosmetic industry and medicine. However, the toxic potential of BAC may be hazardous to humans, due to the common use of preparations containing BAC as a preservative. MATERIAL AND METHODS To assess the possible toxic effects of BAC, two-stage experiments were performed on female Wistar rats. At first, LC50 after a single exposure to BAC aerosol was determined. Then, the animals were exposed to BAC aerosol at 30 mg/m3 for 6 h, and for 3 days (6 h/day). The controls were unexposed rats. Directly after BAC exposure and 18 h afterwards, BALF concentrations were measured of total protein, Clara cell protein, matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), immunoglobulin E (IgE) and cytokines (TF-alpha, IL-6 and MIP-20), lactate dehydrogenase (LDH) and GSH-S-transferase (GST). RESULTS The LC50 value for exposed rats was ca. 53 mg BAC in m3 air for 4 h. All the rats survived single and repeated inhalation exposure to 30 mg/m3 BAC. After single and repeated exposure, lung weight, total protein, HA and LDH activity in BALF of exposed rats were higher than in controls while CC16 levels were decreased. A significantly higher BALF concentration of IL-6 and IgE was noted in animals exposed to single and repeated doses. BALF concentrations of MMP-9, TNF-alpha, and MIP-2 in exposed rats were similar to those in control animals. CONCLUSION BAC may be classified to class I acute inhalation toxicity. It showed a strong inflammatory and irritant activity on the lungs after 6h inhalation and stimulated dynamic patterns of IL-6 and IgE production and protein infiltration from blood vessels to BALF. Continued exposure resulted in cellular destruction, a statistically significant increase in LDH activity and a continuous decrease in CC16 concentration in BALF.

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

BackgroundBenzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC.Materials and MethodsExperiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m3 for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h.ResultsCompared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis.ConclusionInhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs.

The Leiden Mutation and Activated Protein C Resistance as Risk Factors for Disseminated Intravascular Coagulation in Acutely Poisoned Patients

The aim of this work was to assess the prevalence of a genetic predisposition to disseminated intravascular coagulation (DIC) among acutely poisoned patients. Activated protein C resistence (APCR) is a genetically determined cause of thrombophilia and DIC development. One hundred seventy-six subjects were divided into three groups: one consisted of 83 acutely poisoned patients with DIC; a second consisted of 57 acutely poisoned patients without DIC; the third group consisted of 91 healthy controls. Abnormal results of APCR testing were found in 24.1% of the poisoned DIC group, 5.3% of the poisoned nonDIC group, and 3.3% of the control group. Genetic tests were performed in 37 selected patients. Factor V Leiden mutation (G/A genotype) was determined to be present in people whose R index value was below 1.9. These results raise the possibility that outcomes of acute poisonings may be influenced by genetic predisposition.