Correlation of PD-1/PD-L1 Signaling Pathway with Treg/Th17 Imbalance from Asthmatic Children.

BACKGROUND: The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in asthma pathogenesis, but no therapeutic targets could modulate the Th17/Treg balance specifically for asthma. Since previous studies have shown the programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis in this disease, we hypothesized that the PD-1/PD-L1 pathway might be involved in the regulation of Treg/Th17 imbalance in asthmatic children. METHODS: The percentage of Treg and Th17 cells and the expression of PD-1 and PD-L1 were detected by flow cytometry in children with asthma and healthy controls. CD4+ T cells were stimulated with Th17 and Treg differentiating factors, and treated with anti-PD-1. Then cells were harvested and measured for Th17 and Treg percentages and Foxp3 and RORγt levels using RT-PCR. RESULTS: We observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 in the two subsets also changed in the mild persistent and moderate to severe persistent groups compared with healthy controls. In vitro, administration of anti-PD-1 could decrease Th17 percentages and RORγt mRNA, and increase Treg percentages and Foxp3 mRNA in CD4+ T cells of children with asthma in the mild persistent and moderate to persistent groups. Additionally, the role played by anti-PD-1 in regulating Treg/Th17 balance was further confirmed in an asthmatic mouse model. CONCLUSION: Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. Treatment with anti-PD-1 posed protective effects on asthma models, providing a novel theoretical target for asthma.

Effects of propofol versus sevoflurane on cerebral oxygenation and cognitive outcome in patients with impaired cerebral oxygenation.

BACKGROUND: Postoperative neurocognitive dysfunction induced by anesthetics, particularly in elderly patients with impaired oxygenation, is a common complication of surgery and is eliciting increased interest in clinical practice. To investigate the effects of anesthetics on neurocognition, we compared the effects of propofol versus sevoflurane on cerebral oxygenation and cognitive outcome in patients with impaired cerebral oxygenation undergoing general anesthesia. METHODS: Sixty-three patients with impaired cerebral oxygenation (jugular venous bulb oxygen saturation [SjvO2] <50%) or cerebral blood flow/cerebral metabolic rate of oxygen ([CBF/CMRO2] ≤15%) undergoing elective abdominal surgery were randomly allocated into propofol group (group P) or sevoflurane group (group S). The clinical parameters and jugular venous bulb blood gas analysis were monitored throughout the surgical procedure. Cognitive function was assessed with the mini-mental state examination and Montreal Cognitive Assessment at day 1 and day 7 following surgery. S100ß protein in plasma was measured using enzyme-linked immunosorbent assay. RESULTS: The SjvO2 increased during anesthesia induction and surgery when compared to baseline but had no significant difference between group P and group S. When compared to baseline, the CBF/CMRO2 was increased only at the end of surgery and extubation in group P; however, the CBF/CMRO2 in group S was increased during anesthesia induction at 1 hour, 2 hours, end of surgery, and extubation. Furthermore, the CBF/CMRO2 in group S was significantly higher than that in group P during anesthesia induction at 1 hour, 2 hours, and end of surgery. S100ß protein did not significantly change at extubation and 1 day after surgery in both groups when compared to baseline. There was no significant difference in mini-mental state examination and Montreal Cognitive Assessment scores between group P and group S at all time points. CONCLUSION: Sevoflurane showed similar effects in postoperative neurocognitive function as propofol but could improve cerebral oxygenation in patients with impaired cerebral oxygenation.

Intestinal ischaemia/reperfusion upregulates beta-defensin-2 expression and causes acute lung injury in the rat.

OBJECTIVE: Human beta-defensin-2 (BD-2) is a positive ion antimicrobial peptide. We investigated the effects of intestinal ischaemia/reperfusion (II/R) on rat BD-2 mRNA and protein expressions in rat lung to address the potential role of BD-2 in acute lung injury (ALI) induced by II/R. METHODS: Rats were randomly divided into two groups (n=36 each). (i) Sham control and (ii) II/R group (1h superior mesenteric artery clamping, followed by reperfusion of different durations). In II/R group, 6 animals were sacrificed at 0min, 15min, 30min, 60min, 3h and 6h after reperfusion, and serum, lung tissue and bronchoalveolar lavage fluid were harvested. Samples were taken at the corresponding time points in the sham group. Lung histological changes were observed under microscope and the pulmonary permeability index (PPI) was calculated. The lung tissue levels of TNFalpha were detected by ELISA. BD-2 mRNA and protein expressions were examined by RT-PCR and western blotting techniques, respectively. RESULTS: ALI induced by II/R was confirmed by pathological examination and significantly increased PPI (P<0.05 or 0.01). II/R significantly increased the lung TNFalpha levels and upregulated the expressions of BD-2 mRNA and protein expressions (P<0.05 or 0.01). BD-2 mRNA expression was significantly positively correlated to the lung TNFalpha level (r=0.823, P<0.01) and negatively correlated to PPI (r=-0.615, P<0.05). CONCLUSION: II/R can upregulate BD-2 mRNA and protein expressions in rat lung. BD-2 could be an innate protective factor against II/R-induced lung injury.