Proteolysis-inducing factor differentially influences transcriptional regulation in endothelial subtypes.
Proteolysis-inducing factor (PIF) is a novel sulfated 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 SK-HEP-1 and in human umbilical vein endothelial cells (HUVECs) but not in pulmonary artery endothelial cells. PIF differentially induces activation of nuclear factor-kappaB, resulting in the induction of proinflammatory cytokines [interleukin (IL)-8 and IL-6] and increased expression of the cell surface proteins intercellular adhesion molecule-1 and vascular cell adhesion molecule 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 proinflammatory response observed in cancer cachexia but may also have a role without the cachectic process.
Watchorn
T M
TM
Molecular Immunology Group, Department of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh EH3 9YW, United Kingdom.
Waddell
I
I
Ross
J A
JA
D001798:Blood Proteins / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D004727:Endothelium / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011509:Proteoglycans / Q000032:analysis; D011651:Pulmonary Artery; D053669:Syndecan-2; D053667:Syndecans; D014158:Transcription, Genetic / Q000187:drug effects; D025801:Ubiquitin / Q000378:metabolism; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D001798:Blood Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011509:Proteoglycans; C508245:SDC2 protein, human; D053667:Syndecans; D025801:Ubiquitin; D019010:Vascular Cell Adhesion Molecule-1; C042057:proteolysis-inducing peptide; D018799:Intercellular Adhesion Molecule-1; D053669:Syndecan-2