Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation

INTRODUCTION: Although the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure. MATERIALS AND METHODS: Plastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups. RESULTS: The results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4+ T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p < 0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group. CONCLUSION: The asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases

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Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation.

INTRODUCTION: Although the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure. MATERIALS AND METHODS: Plastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups. RESULTS: The results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4+ T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p<0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group. CONCLUSION: The asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases.

Ventricular dilatation in experimental intraventricular hemorrhage in pigs. Characterization of cerebrospinal fluid dynamics and the effects of fibrinolytic treatment.

BACKGROUND AND PURPOSE: Hemorrhagic ventricular dilatation (HVD) is a prominent feature of human intraventricular hemorrhage (IVH) and a strong indicator for poor outcome. We developed an IVH model to define the mechanisms responsible for HVD and to test the efficacy of intraventricular administration of tissue plasminogen activator (TPA) in the treatment of HVD. METHODS: Isolated IVH was produced in pigs by injecting 10 mL of blood simultaneously with thrombin into the right lateral ventricle. The treatment group received 1.5 mg of TPA after induction of IVH. Intraventricular blood volume and the volume of the lateral ventricles were assessed by CT after 90 minutes, 7 days, and 42 days. Intracranial pressure, the pressure-volume index, and the resistance to outflow of cerebrospinal fluid (R(out)) were measured 30 minutes and 7 days after IVH. RESULTS: After IVH, the volume of the lateral ventricles increased from 1.98 +/- 0.69 to 6.43 +/- 1.23 mL (P < .001). There was a linear relationship between ventricular and clot volume (P = .014). Initially, R(out) increased from 24.34 +/- 7.13 to 63.56 +/- 64.91 mm Hg/mL per minute (P < .001). After 7 days, restoration of normal cerebrospinal fluid circulation occurred, but the ventricles were still significantly enlarged (5.24 +/- 1.76 mL, P < .001) and filled with blood. Within 6 weeks, ventricular volume had returned to normal values, paralleled by complete clot resolution. Intraventricular administration of TPA significantly accelerated clot clearance and restoration of normal ventricle volume. CONCLUSIONS: These results suggest that intraventricular bleeding may cause impairment of cerebrospinal fluid circulation but that the mass effect of clots distending the ventricle walls is the most important mechanism responsible for HVD. This model closely imitates several prominent features of human IVH and may therefore be a useful tool for preclinical assessment of the efficacy and safety of treatment with TPA.

PET-study of intracranial meningiomas: correlation with histopathology, cellularity and proliferation rate.

The glucose metabolism of 62 meningiomas was measured by fluorine -18-2-fluorodeoxyglucose (FDG) PET and correlated with proliferation rate (Ki-67 index) and tumor cellularity. The mean metabolic rate (MRGlu) for meningiomas was 0.26 +/- 0.13 mikromol/g/min (range 0.08-0.62 mikromol/g/min). The relative tumor FDG-uptake (Q-MRGlu) (tumor/contralateral cortex) of all meningiomas was calculated with 0.73 +/- 0.37 (0.24-1.79). Differences of Q-MRGlu were significant between the groups with high vs. low cellularity (p < 0.01), increased vs. normal proliferation rate (p < 0.025) and low (WHO grade I) vs. higher (WHO grades II, III) graded tumors. In recurrent meningiomas (14 tumors) the glucose metabolism was not increased. The data show that 18 FDG-PET is suitable to serve as non-invasive predictor of tumor growth characteristics in meningiomas.