Figure 5.IL-1α upregulates miR-146a in senescent cells.(A)
Northern analysis for miR-146a levels in damage-induced senescent HCA2
cells treated with neutralizing antibodies against IL1-α and
IL1-β. HCA2 cells (PD 35) were used and induced to senesce by
treatment with bleomycin. Cells were harvested for RNA 11 days later.
Details of the procedure are described in ‘Experimental Procedures. (B)
Western analysis for IL-6 in damage-induced senescent HCA2 cells treated
with neutralizing antibodies to IL-1α and IL-1β. CM were
harvested 11 days after bleomycin treatment. (C) Model for the role
of miR-146a/b in senescent cells: In response to a high SASP (right
branch), IL-1α interacts with the IL-1α receptor (IL-1αR)
and the signaling pathway that involves IRAK1 is fully activated. This
activation leads to the well-documented activation of the transcription
factor NFкB and production of IL-6, IL-8 and also miRNA-146a/b.
miRNA-146a/b is a component of a negative feedback loop and acts to
downregulate the levels of IRAK1, hence restraining the levels of IL-6 and
IL8. However, in response to a low SASP (left branch), the signaling
pathway is not sufficiently activated. Thus there is a low level of IL-6
and IL-8 secretion and miRNA-146a/b is not upregulated.
