Research Paper Volume 1, Issue 4 pp 402—411

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.