Open AccessPost-transcriptional regulation of interleukin 1 alphain various strains of young and senescent human umbilical vein endothelialcells.
Author(s) -
Susan Garfinkel,
Sondi Brown,
J Wessendorf,
Thomas Maciag
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.4.1559
Subject(s) - umbilical vein , senescence , biology , messenger rna , cytokine , microbiology and biotechnology , alpha (finance) , gene expression , endocrinology , medicine , in vitro , immunology , gene , biochemistry , construct validity , nursing , patient satisfaction
Human umbilical vein endothelial cell (HUVEC)senescence in vitro is characterized by the loss of proliferative potential andan increase in cell size. Because HUVEC senescence in one strain (H101) has beencharacterized by the increase in the steady-state mRNA level for thesignal-peptideless cytokine, interleukin (IL) 1 alpha, we have examined youngand senescent populations of five additional HUVEC strains (H3605, H103, H928,H929, and H930) to determine whether the elevated levels of IL-1 alpha mRNAcould be observed in all HUVEC strains. Consistent with the data from strainH101, strains H3605 and H930 also exhibited a low steady-state level of the IL-1alpha mRNA in young populations compared to elevated levels of IL-1 alpha mRNAin the senescent populations. However, three strains (H103, H928, and H929) didnot exhibit reduced levels of IL-1 alpha mRNA in the young populations, andinterestingly, strain H928, at times, expressed relatively high IL-1 alpha mRNAlevels in the young populations. In addition, expression of the steady-statelevel of plasminogen activator inhibitor 1 and cyclooxygenase 2 was elevated insenescent populations of all HUVEC strains examined, whereas young populationsexhibited a low level of expression for these genes regardless of the IL-1 alphamRNA level. Further, the level of the IL-1 alpha polypeptide was elevated insenescent HUVEC populations relative to young populations that expressed eithera high or low level of the IL-1 alpha mRNA. We have also demonstrated that theelevated level of IL-1 alpha mRNA in the senescent population of strain H3605may be regulated by mRNA stability; however, this mechanism does not apply toall the HUVEC strains examined in this study. Thus, we suggest that while mRNAlevels of the IL-1-response genes for plasminogen activator inhibitor 1 andcyclooxygenase 2 are appropriate markers for HUVEC senescence, HUVECstrain-specific post-transcriptional mechanisms may exist to regulate thefunction of IL-1 alpha as a modifier of HUVEC senescence invitro.