Post-transcriptional regulation of interleukin 1 alpha in various strains of young and senescent human umbilical vein endothelial cells.

Human umbilical vein endothelial cell (HUVEC) senescence in vitro is characterized by the loss of proliferative potential and an increase in cell size. Because HUVEC senescence in one strain (H101) has been characterized by the increase in the steady-state mRNA level for the signal-peptideless cytokine, interleukin (IL) 1 alpha, we have examined young and senescent populations of five additional HUVEC strains (H3605, H103, H928, H929, and H930) to determine whether the elevated levels of IL-1 alpha mRNA could be observed in all HUVEC strains. Consistent with the data from strain H101, strains H3605 and H930 also exhibited a low steady-state level of the IL-1 alpha mRNA in young populations compared to elevated levels of IL-1 alpha mRNA in the senescent populations. However, three strains (H103, H928, and H929) did not exhibit reduced levels of IL-1 alpha mRNA in the young populations, and interestingly, strain H928, at times, expressed relatively high IL-1 alpha mRNA levels in the young populations. In addition, expression of the steady-state level of plasminogen activator inhibitor 1 and cyclooxygenase 2 was elevated in senescent populations of all HUVEC strains examined, whereas young populations exhibited a low level of expression for these genes regardless of the IL-1 alpha mRNA level. Further, the level of the IL-1 alpha polypeptide was elevated in senescent HUVEC populations relative to young populations that expressed either a high or low level of the IL-1 alpha mRNA. We have also demonstrated that the elevated level of IL-1 alpha mRNA in the senescent population of strain H3605 may be regulated by mRNA stability; however, this mechanism does not apply to all the HUVEC strains examined in this study. Thus, we suggest that while mRNA levels of the IL-1-response genes for plasminogen activator inhibitor 1 and cyclooxygenase 2 are appropriate markers for HUVEC senescence, HUVEC strain-specific post-transcriptional mechanisms may exist to regulate the function of IL-1 alpha as a modifier of HUVEC senescence in vitro.