Related resources
Full-text held externally
- DOI: 10.1111/j.1476-5381.2008.00129.x
- PMID: 19298391
- UKPMCID: 19298391
Search for item elsewhere
University researcher(s)
Academic department(s)
Transport of interleukin-1 across cerebromicrovascular endothelial cells.
Skinner, R A; Gibson, R M; Rothwell, N J; Pinteaux, E; Penny, J I
British journal of pharmacology. 2009;156(7):1115-23.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- DOI: 10.1111/j.1476-5381.2008.00129.x
- PMID: 19298391
- UKPMCID: 19298391
Abstract
BACKGROUND AND PURPOSE: The inflammatory cytokine interleukin-1 (IL-1) has profound actions in the brain, causing neuronal cell death and exacerbating brain damage. While circulating levels are normally low, IL-1 can be produced on the vascular side of the brain endothelium, and within the brain. The naturally occurring IL-1 receptor antagonist has been administered peripherally in a Phase II trial in acute stroke patients; understanding how IL-1 and IL-1 receptor antagonist penetrate the brain is, therefore, of considerable importance. EXPERIMENTAL APPROACH: An in vitro blood-brain barrier model was generated by co-culture of porcine brain microvascular endothelial cells with astrocytes. The mechanisms of transcellular transport of IL-1beta and IL-1 receptor antagonist were characterized in this model, using endocytosis inhibitors and IL-1 receptor-blocking antibodies. KEY RESULTS: Transcellular IL-1beta and IL-1 receptor antagonist transport was temperature-dependent and IL-1beta was transported with higher affinity than IL-1 receptor antagonist. IL-1beta inhibited IL-1 receptor antagonist transport more potently than IL-1 receptor antagonist inhibited IL-1beta transport. Transport of IL-1beta and IL-1 receptor antagonist was not via adsorptive-mediated endocytosis, although inhibition of microtubule assembly significantly attenuated transport of both cytokines. An antibody directed to the type II IL-1 receptor significantly reduced IL-1beta transport. CONCLUSIONS AND IMPLICATIONS: These results are consistent with IL-1 and IL-1 receptor antagonist being transported across cultured cerebromicrovascular endothelial cells and suggest that IL-1beta transport may occur via a type II IL-1 receptor-dependent mechanism. Understanding IL-1 transport into the brain may have benefits, particularly in enhancing penetration of IL-1 receptor antagonist into the brain.