NF-κB regulates the response of embryonic cells to heat shock

NF-κB was shown previously to regulate apoptotic cell death processes in various experimental systems. However, its role in controlling teratogen-induced cell death has not been established yet. Therefore, the objective of the present study was to explore the involvement of the p65 subunit of NF-κB in the response of mouse embryonic fibroblasts (MEFs) to heat shock, using p65 knockout (p65^-/-) cells. Indeed, we found p65^-/- MEFs to be more susceptible to the exposure to heat shock, as compared with wild-type (WT) MEFs, as they demonstrated a more prominent decrease in cell survival and proliferation as well as the appearance of cells undergoing apoptotic cell death. These heat-shock-induced effects were preceded by a decrease in p65 expression in WT cells, which was accompanied by a decrease in IκBα expression in WT MEFs, while disappearing completely in p65^-/- MEFs and accordingly, by an increase in p-IκBα expression in both cell lines, which was found to be more prominent in p65-/- MEFs. Interestingly, the heat shock-induced decrease in p65 expression was accompanied by an increase in HSP70 expression in both cell lines. However, it was again found to be more prominent in p65^-/- MEFs. Taken together, our results suggest a protective role for the p65 subunit of NF-κB in mechanisms underlying the response of embryonic cells to heat shock.