Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49388
Title: GENOTOXIC STRESS INDUCES CASPASE-DEPENDENT IL-1RA SECRETION
Authors: CHWEE JYH YUN
Keywords: Interleukin-1, Interleukin-1 receptor antagonist, Inflammation, Caspase, Genotoxic stress, Apoptosis
Issue Date: 14-Aug-2013
Source: CHWEE JYH YUN (2013-08-14). GENOTOXIC STRESS INDUCES CASPASE-DEPENDENT IL-1RA SECRETION. ScholarBank@NUS Repository.
Abstract: Cells are commonly exposed to genotoxic stress and have therefore evolved mechanisms to initiate the DNA damage response (DDR). If the DNA damage is too extensive to be repaired however, the cell undergoes apoptosis. Recent studies suggest that persistent DNA damage induces cells to senesce and upregulate cytokines such as interleukin (IL)-1, however, the immediate effects of genotoxic stress on cytokine secretion are still not well understood. Here, we report that genotoxic stress caused by bleomycin activates DDR and induces damaged cells to enter apoptosis. Bleomycin induces IL-1Ra secretion within 24 h but not IL-1 or IL-1R. Interestingly, our data indicate that bleomycin-induced IL-1Ra expression is mediated via non-classical secretory pathway. We have also shown that bleomycin-induced IL-1Ra secretion is regulated by caspase activation and can impair IL-1-induced IL-6 gene expression, suggesting that the immediate response of damaged cells to genotoxic stress is to dampen inflammatory responses by secreting IL-1Ra.
URI: http://scholarbank.nus.edu.sg/handle/10635/49388
Appears in Collections:Ph.D Theses (Open)

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