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EN
Leukocyte adhesion to the vascular endothelium contributes to many immunological and inflammatory disorders. These processes have been shown to be mediated by bradykinin receptor type 2 (B2R) and dopamine receptor type 2 (D2R). In a previous study, we reported the formation of a B2R-D2R heterodimer, possibly altering cellular functions. Hence, in the present study, we examined the effect of co-activation of endothelial cells with B2R and D2R agonists on the interaction of these cells with neutrophils. Bradykinin, the main B2R agonist, significantly increased cell adhesion, and this effect was reversed when the endothelial cells were additionally co-treated with a selective D2R agonist, sumanirole. These results were dependent on the incubation time, showing an opposite tendency after prolonged stimulation. Significant changes in the expression of adhesion proteins, such as E-selectin and intercellular adhesion molecule 1 in endothelial cells were observed. Additionally, the cells preincubated with tumor necrosis factor-α showed decreased cell adhesion and IL-8 release after long incubation with both agonists. The modulation of cell adhesion by D2R and B2R seem to be mediated via STAT3 phosphorylation. In summary, this study demonstrated a protective role of D2R in neutrophil-endothelial cell adhesion induced by bradykinin, especially in cytokine-stimulated endothelial cells.
EN
Obtaining a suitable experimental cellular model is a major problem for neuroscience studies. Neuroblastoma cell lines have been often applied in studies related to pathological disorders of nervous system. However, in the search for an ideal model, these cells must be differentiated to cancel their tumor character. The subsequent reactions that are caused by differentiation are not always indifferent to the same model. We evaluated the effect of two well known substances, used for SH-N-SK cell line differentiation, retinoic acid (RA) and phorbol-12-myristate-13-acetate (PMA), on the induction of pro-inflammatory and pro-oxidative reactions in these cells. Cells differentiated with PMA were able to produce significantly higher amounts of pro-inflammatory cytokines whereas the release of nitric oxide radicals was similar to that in undifferentiated cells. On the contrary, in RA-differentiated cells no significant changes in cytokine production were observed and the nitric oxide release was decreased. Additionally, the RA-differentiated neuronal model was more sensible to lipopolysaccharide stimulation, producing pro-inflammatory cytokines abundantly. These results suggest that RA-differentiated SH-N-SK cells provide a more suitable experimental model for the study of molecular and cellular mechanisms of the inflammation and oxidative stress in neuronal cells.
EN
The G protein-coupled receptors (GPCRs), one of the largest protein families, are essential components of the most commonly used signal-transduction systems in cells. These receptors, often using common pathways, may cooperate in the regulation of signal transmission to the cell nucleus. Recent scientific interests increasingly focus on the cooperation between these receptors, particularly in a context of their oligomerization, e.g. the formation of dimers that are able to change characteristic signaling of each receptor. Numerous studies on kinin and dopamine receptors which belong to this family of receptors have shown new facts demonstrating their direct interactions with other GPCRs. In this review, current knowledge on signaling pathways and oligomerization of these receptors has been summarized. Owing to the fact that kinin and dopamine receptors are widely expressed in cell membranes where they act as mediators of numerous common physiological processes, the information presented here sheds new light on a putative crosstalk of these receptors and provides more comprehensive understanding of possible direct interactions that may change their functions. The determination of such interactions may be useful for the development of new targeted therapeutic strategies against many disorders in which kinin and dopamine receptors are involved.
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