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Chromatin regulates IL-33 release and extracellular cytokine activity.


ABSTRACT: IL-33 is an epithelium-derived, pro-inflammatory alarmin with enigmatic nuclear localization and chromatin binding. Here we report the functional properties of nuclear IL-33. Overexpression of IL-33 does not alter global gene expression in transduced epithelial cells. Fluorescence recovery after photobleaching data show that the intranuclear mobility of IL-33 is ~10-fold slower than IL-1?, whereas truncated IL-33 lacking chromatin-binding activity is more mobile. WT IL-33 is more resistant to necrosis-induced release than truncated IL-33 and has a relatively slow, linear release over time after membrane dissolution as compared to truncated IL-33 or IL-1?. Lastly, IL-33 and histones are released as a high-molecular weight complex and synergistically activate receptor-mediated signaling. We thus propose that chromatin binding is a post-translational mechanism that regulates the releasability and ST2-mediated bioactivity of IL-33 and provide a paradigm to further understand the enigmatic functions of nuclear cytokines.

SUBMITTER: Travers J 

PROVIDER: S-EPMC6092330 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Chromatin regulates IL-33 release and extracellular cytokine activity.

Travers Jared J   Rochman Mark M   Miracle Cora E CE   Habel Jeff E JE   Brusilovsky Michael M   Caldwell Julie M JM   Rymer Jeffrey K JK   Rothenberg Marc E ME  

Nature communications 20180814 1


IL-33 is an epithelium-derived, pro-inflammatory alarmin with enigmatic nuclear localization and chromatin binding. Here we report the functional properties of nuclear IL-33. Overexpression of IL-33 does not alter global gene expression in transduced epithelial cells. Fluorescence recovery after photobleaching data show that the intranuclear mobility of IL-33 is ~10-fold slower than IL-1α, whereas truncated IL-33 lacking chromatin-binding activity is more mobile. WT IL-33 is more resistant to ne  ...[more]

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