10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Cytokines and neutrophils as important mediators of platelet-activating factor-induced kinin B1 receptor expression.

      British Journal of Pharmacology
      Animals, Cytokines, biosynthesis, physiology, Edema, pathology, Interleukin-1, Male, NF-kappa B, Neutrophil Infiltration, drug effects, Neutrophils, Peroxidase, metabolism, Platelet Activating Factor, pharmacology, RNA, Messenger, Rats, Rats, Wistar, Receptor, Bradykinin B1, Time Factors, Tumor Necrosis Factor-alpha, Up-Regulation

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          PAF injection into the rat paw is accompanied by the concomitant activation of NF-kappaB and neutrophil influx, which appears to be relevant to the up-regulation of kinin B1 receptors. Herein, we analyse the role of TNF-alpha and IL-1beta production for PAF-induced B1 receptor upregulation in the rat paw. Additionally, we evaluate how cytokine production and neutrophil migration fit into the temporal sequence of events leading to PAF-induced B1 receptor upregulation. In our experiments, treatment with PAF resulted in a marked increase of B1 receptor-mediated paw oedema and in situ production of TNF-alpha at 1 h and IL-1beta at 3 and 6 h later. B1 receptor-mediated paw oedema was significantly inhibited by anti-TNF-alpha antibody and by interleukin-1 receptor antagonist (IRA). TNF-alpha was necessary for the local PAF-induced IL-1beta production. NF-kappaB blocker PDTC prevented the production of both TNF-alpha and IL-1beta, indicating that cytokine production is NF-kappaB dependent. Depletion of neutrophils with an anti-PMN antibody prevented IL-1beta, but not TNF-alpha, production. Although both TNF-alpha and IL-1beta are relevant to functional B1 receptor upregulation, PAF-induced increase in B1 receptor mRNA was markedly suppressed by anti-TNF-alpha and, to a lesser extent, by IRA. B1 receptor mRNA expression was also prevented by the anti-PMN antibody. In conclusion, the activation of the TNF-alpha/neutrophil axis by PAF seems to be sufficient for B1 receptor mRNA production. However, the TNF-alpha/neutrophil axis is also necessary for IL-1beta production. These two processes might lead to the appearance of functional kinin B1 upregulation receptors in vivo after PAF treatment.

          Related collections

          Author and article information

          Comments

          Comment on this article