Kynurenic acid and its derivatives are able to modulate the adhesion and locomotion of brain endothelial cells
8 ungerska forskare från Semmelweis Uni och Szeged Uni har fått denna rapport godkänd och publicerad i Springer Nature publikationen Journal of Neural Transmission. 2018-01-13
Abstract
The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in several neurodegenerative disorders [characterized by damage to the cerebral endothelium and to the blood–brain barrier (BBB)] are well established. Cell–extracellular matrix (ECM) adhesion is supposedly involved in recovery of impaired cerebral endothelium integrity (endothelial repair). The present work aimed to investigate the effects of KYNA and its synthetic derivatives on cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8 rat brain endothelial cell line, modeling the BBB endothelium. The effects of KYNA and its derivatives on cell adhesion were measured using an impedance-based technique, the xCELLigence SP system. Holographic microscopy (Holomonitor™ M4) was used to analyse both chemokinetic responses and morphometry. The GP8 cells proved to be a suitable model cell line for investigating cell adhesion and the locomotion modulator effects of kynurenines. KYNA enhanced cell adhesion and spreading, and also decreased the migration/motility of GP8 cells at physiological concentrations (10−9 and 10−7 mol/L). The derivatives containing an amide side-chain at the C2 position (KYNA-A1 and A2) had lower adhesion inducer effects compared to KYNA. All synthetic analogues (except KYNA-A5) had a time-dependent inhibitory effect on GP8 cell adhesion at a supraphysiological concentration (10−3 mol/L). The immobilization promoting effect of KYNA and the adhesion inducer activity of its derivatives indicate that these compounds could contribute to maintaining or restoring the protective function of brain endothelium; they also suggest that cell–ECM adhesion and related cell responses (e.g. migration/motility) could be potential new targets of KYNA.
The effects of KYNA and its derivatives on cell adhesion were measured using an
impedance-based technique, the xCELLigence SP system. Holographic microscopy
(Holomonitor™ M4) was used to analyse both chemokinetic responses and morphometry
impedance-based technique, the xCELLigence SP system. Holographic microscopy
(Holomonitor™ M4) was used to analyse both chemokinetic responses and morphometry
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14 kinesiska forskare har fått sin rapport godkänd och publicerad i publikationen American Journal of Physiology Society.
2018-01-11
β-Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release
Abstract
Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. Emerging evidence indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increases acute inflammation and contributes to the development of ALI. Even though numerous studies have increased our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, emphasizing that there is an urgent need for novel treatment strategies. In this study, a new series of small compounds of β-nitrostyrene derivatives (BNSDs) were synthesized and their anti-inflammatory bioactivities on neutrophils and platelets were evaluated. The new small compound C7 modulates neutrophil function by inhibiting superoxide generation and elastase release. Compound C7 elicits protective effects on LPS-induced paw edema and acute lung injury via the inhibition of neutrophil accumulation, pro-inflammatory mediator release, platelet aggregation, myeloperoxidase activity and neutrophil extracellular trap (NET) release. NET formation was identified as the bridge for the critical interactions between neutrophils and platelets by confocal microscopy and flow cytometry. This research provides new insights for elucidating the complicated regulation of neutrophils and platelets in ALI and sheds further light on future drug development strategies for ALI/ARDS and acute inflammatory diseases.
… Phase holographic image analysis. The time-lapse videos and cell morphology 331 images were recorded with a HoloMonitor M4 (Phase Holographic Imaging AB, Lund, 332 Sweden) to assess the effects of the compound on neutrophil-platelet interaction and 333 activation …
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