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Am J Physiol Endocrinol Metab (December 4, 2001). doi:10.1152/ajpendo.00408.2001
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Articles in PresS, published online ahead of print December 4, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00408.2001
Submitted on September 14, 2001
Accepted on November 22, 2001

Proteolysis Inducing Factor Differentially Influences Transcriptional Regulation in Endothelial Subtypes

Tammy M Watchorn1, Ian Waddell2, and James A Ross1*

1 Clinical & Surgical Sciences, University of Edinburgh, Edinburgh, Lothian, United Kingdom
2 CV & GI Discovery, Astra Zeneca, Macclesfield, Cheshire, United Kingdom

* To whom correspondence should be addressed. E-mail: jr{at}srv2.med.ed.ac.uk.

Proteolysis inducing factor (PIF) is a novel sulphated glycoprotein initially identified as a protein capable of triggering muscle proteolysis during the process of cancer cachexia. Only skeletal muscle and liver exhibit substantial binding of PIF in adult tissue. Here we demonstrate that PIF induces transcriptional regulation in both the liver endothelial cell line, SKHep-1, and in HUVECs, but not in pulmonary artery endothelial cells. PIF differentially induces activation of NF-{kappa}B resulting in the induction of pro-inflammatory cytokines (IL-8 and IL-6) and increased expression of the cell surface proteins ICAM-1 and VCAM in SK-Hep-1 and HUVECs only. In addition, PIF induces the shedding of syndecans from the cell surface. Syndecans are involved in wound repair, metastasis of cancers and embryonic development. These results suggest that PIF may play additional roles in the pro-inflammatory response observed in cancer cachexia but may also have a role outwith the cachectic process.




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