Interleukin-1 receptor antagonist (IL-1ra) modulates endothelial cell proliferation.
Endothelial cell (EC) lifespan controlled by the IL-1 family of cytokines is an important determinant of susceptibility to artery wall disease. Here we show that EC lacking intracellular interleukin-1 receptor antagonist (IL-1ra) have a reduced lifespan compared to controls. Over expression of IL-1ra enhanced proliferation via cyclin dependent kinase 2 activity and retinoblastoma protein phosphorylation. This was not seen in EC lacking IL-1 receptor 1 (IL-1 signalling ability), nor apparent using other stimuli e.g. TNF alpha. These data suggest that IL-1ra has a specific and receptor-dependent function to control the growth and lifespan of EC.
Dewberry
Rachael M
RM
Cardiovascular Research Unit, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2RX, United Kingdom. r.dewberry@sheffield.ac.uk <r.dewberry@sheffield.ac.uk>
King
Andrea R
AR
Crossman
David C
DC
Francis
Sheila E
SE
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D016160:Retinoblastoma Protein / Q000378:metabolism
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D016160:Retinoblastoma Protein; D051357:Cyclin-Dependent Kinase 2