POSTTRANSCRIPTIONAL 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 c haracterized by the loss of proliferative potential and an increase in cell size. Because HUVEC senescence in one strain (H101) has been cha racterized by the increase in the steady-state mRNA level for the sign al-peptideless cytokine, interleukin (IL) 1 alpha, we have examined yo ung 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 c ompared to elevated levels of IL-1 alpha mRNA in the senescent populat ions. However, three strains (H103, H928, and H929) did not exhibit re duced levels of IL-1 alpha mRNA in the young populations, and interest ingly, strain H928, at times, expressed relatively high IL-1 alpha mRN A levels in the young populations. In addition, expression of the stea dy-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 th ese genes regardless of the IL-1 alpha mRNA level. Further, the level of the IL-1 alpha polypeptide was elevated in senescent HUVEC populati ons relative to young populations that expressed either a high or low level of the IL-1 alpha mRNA. We have also demonstrated that the eleva ted level of IL-1 alpha mRNA in the senescent population of strain H36 05 may be regulated by mRNA stability; however, this mechanism does no t apply to all the HUVEC strains examined in this study. Thus, we sugg est 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 mechanis ms may exist to regulate the function of IL-1 alpha as a modifier of H UVEC senescence in vitro.