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- W4313373110 abstract "Abstract Interferon regulatory factor 1 (IRF1) is a transcription factor that is induced in response to interferons and inflammatory cytokines. We have previously identified the role of IRF1 in mediating inflammasome activation. These inflammasomes are associated with providing protective responses against colorectal tumorigenesis. The relevance of IRF1 to the immunobiology of cancer is still emerging, and the crucial role of IRF1 in colorectal cancer (CRC) remains unknown. The multiple inflammatory mediators produced during colorectal tumorigenesis have the ability to mediate cellular death; this may represent alternative forms of apoptosis that cannot readily be recapitulated in vitro by using classical apoptosis inducers. The precise regulatory mechanisms by which IRF1 governs the activation of cell death in response to inflammatory milieu remains elusive. Given that IRF1 is a transcription factor, it may induce the expression of upstream cell death mediators that are dependent on cytokines and that subsequently activate the executioner caspases. Here, we found that Irf1−/− mice were hyper-susceptible to CRC. IRF1 played roles in both myeloid and epithelial compartments to confer protection against CRC. Interestingly, IRF1 did not regulate inflammatory cytokines production and inflammasome activation in colons. However, IRF1 promoted cell death mediated by the inflammatory cytokines. The decreased cell death in the colons of Irf1−/− mice was associated with impaired activation of apoptotic caspases. Mechanistically, we demonstrated that IRF1 deficiency attenuated the induction of Fas and activation of caspase-8 that lead to reduced effector caspase-3 and caspase-7 activation in the colons." @default.
- W4313373110 created "2023-01-06" @default.
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- W4313373110 creator A5074251335 @default.
- W4313373110 creator A5079920356 @default.
- W4313373110 date "2020-05-01" @default.
- W4313373110 modified "2023-09-27" @default.
- W4313373110 title "IRF1 regulates apoptotic caspases to thwart the development of colorectal cancer" @default.
- W4313373110 doi "https://doi.org/10.4049/jimmunol.204.supp.242.33" @default.
- W4313373110 hasPublicationYear "2020" @default.
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