The human diploid fibroblast senescence pathway is independent of interleukin-1 alpha mRNA levels and tyrosine phosphorylation of FGFR-1 substrates.
In vitro cellular senescence of human umbilical vein endothelial cells (HUVEC) may involve the intracellular activity of the signal peptide-less cytokine interleukin (IL)-1 alpha. To determine whether senescence of other human diploid cells involves the function of IL-1 alpha, we examined the steady-state expression of IL-1 alpha mRNA in IMR-90 fibroblasts. The IL-1 alpha transcript was not elevated in senescent IMR-90 cells. With the exception of the plasminogen activator inhibitor (PAI)-1 transcript, other IL-1 alpha-response gene mRNAs were not induced in senescent IMR-90, although the mRNA for each gene was induced by exogenous IL-1 alpha. The mRNA expression of cell cycle-specific genes demonstrated that Fos and ornithine decarboxylase (ODC) were induced in young and senescent cells in response to both serum and fibroblast growth factor (FGF)-1. Histone (H)3 mRNA was induced by serum in young cells, but not in senescent cells, and FGF-1 failed to induce H3 mRNA in either young or senescent cells. Further, while young IMR-90 populations were able to respond to serum as an initiator of DNA synthesis and cell growth, they did not exhibit a response to exogenous FGF-1. FGF receptor (R)-1 substrates were not tyrosine phosphorylated in either young or senescent IMR-90 cells. These data demonstrate that IL-1 alpha and FGF-1 may have different functions in HUVEC and IMR-90 fibroblast populations including distinct pathways for the regulation of cellular growth and senescence.
Garfinkel
S
S
Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, MD 20855, USA.
Wessendorf
J H
JH
Hu
X
X
Maciag
T
T
D016922:Cellular Senescence; D004171:Diploidy; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D010766:Phosphorylation; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D007375:Interleukin-1; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D014443:Tyrosine; D005346:Fibroblast Growth Factors; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1