The active form of NFB2 and c Jun could be seen in the nucleus under normoxic, but not under hypoxic conditions. THP 1, HL 60, and U937 cells express HIF 1a in the cell nucleus under hypoxic and normoxic conditions Myeloid cell selleck chemicals lines are often used as an experimental model for primary human monocytes. We considered in which cellular compartment HIF 1a could be found in unstimulated and PMA stimulated myeloid cell lines under hypoxic conditions. We identified HIF 1a in the nucleus both under nor moxic and hypoxic conditions with or without PMA sti mulation. We conclude that in this regard, the cell lines clearly differ from primary human monocytes and behave like hMDMs. This is of concern as these cell lines, but not human monocytes, Inhibitors,Modulators,Libraries are routinely used for research on bioenergetic issues.

Discussion Circulating blood monocytes face oxygen concentrations of more than 40 mmHg, which fuel oxidative phosphory lation. However, upon migration to inflamed Inhibitors,Modulators,Libraries joints, monocytes encounter hypoxic conditions and must adapt immediately to the reduced pO2. For several different cell types, it has been shown that the transcription factor HIF 1 under hypoxic conditions is translocated into the nucleus where it binds to promoter regions of target genes. This enables cells to adapt and maintain their basic and specific functions. Elbarghati et al. reported recently that primary human macrophages but not monocytes rapidly up regulate HIF 1a and HIF 2a proteins upon exposure to hypoxia, Inhibitors,Modulators,Libraries with translocation of these proteins into the nucleus.

We demonstrate here that the transcription factor HIF 1a also accumulates in quiescent human monocytes under hypoxia, Inhibitors,Modulators,Libraries but is present solely in the cytosol. For this reason, we postulate that it cannot be responsible for the transcriptional induction of typical hypoxia target genes in the nucleus. It is not clear why monocytes differ in this regard from many other cell types, where HIF 1a under hypoxia is translocated into the nucleus. One possibility is that the HIF induced adaptation mechanism in monocytes is not necessary because of the plentiful oxygen supply present in peripheral blood. The stabilisation of HIF 1a in the cytosol under hypoxic con ditions may, therefore, reflect a pre active state that becomes active Inhibitors,Modulators,Libraries when the cells start their migration into low oxygen tissue areas.

However, it should be noted that we also studied quiescent and PHA stimulated peripheral human blood CD3 CD4 T cells, which also circulate in oxygen rich blood. In contrast to monocytes, hypoxic conditions induced HIF 1a in these cells, with transloca tion into the nucleus as shown by immunoblotting. From this observation, we suggest several that the HIF 1a regu lation mechanism may be a feature of the evolutionary younger cells of the adaptive immune system, but not of evolutionary older cells of the innate immune system, such as monocytes.