PMID:22215666

Citation	Kakkar, R, Hei, H, Dobner, S and Lee, RT (2012) Interleukin 33 as a mechanically responsive cytokine secreted by living cells. J. Biol. Chem. 287:6941-8
Abstract	Interleukin 33 (IL-33), a member of the Interleukin 1 cytokine family, is implicated in numerous human inflammatory diseases such as asthma, atherosclerosis, and rheumatoid arthritis. Despite its pathophysiologic importance, fundamental questions regarding the basic biology of IL-33 remain. Nuclear localization and lack of an export signal sequence are consistent with the view of IL-33 as a nuclear factor with the ability to repress RNA transcription. However, signaling via the transmembrane receptor ST2 and documented caspase-dependent inactivation have suggested IL-33 is liberated during cellular necrosis to effect paracrine signaling. We determined the subcellular localization of IL-33 and tracked its intracellular mobility and extracellular release. In contrast to published data, IL-33 localized simultaneously to nuclear euchromatin and membrane-bound cytoplasmic vesicles. Fluorescent pulse-chase fate-tracking documented dynamic nucleo-cytoplasmic flux, which was dependent on nuclear pore complex function. In murine fibroblasts in vitro and in vivo, mechanical strain induced IL-33 secretion in the absence of cellular necrosis. These data document IL-33 dynamic inter-organelle trafficking and release during biomechanical overload. As such we recharacterize IL-33 as both an inflammatory as well as mechanically responsive cytokine secreted by living cells.
Links	PubMed PMC3307313 Online version:10.1074/jbc.M111.298703
Keywords	Adenosine Triphosphate/metabolism; Animals; Cell Nucleus/metabolism; Cytoplasm/metabolism; Gene Transfer Techniques; Humans; Interleukin-33; Interleukins/genetics; Interleukins/physiology; Interleukins/secretion; Male; Mice; Mice, Inbred C57BL; Microtubules/metabolism; Myocytes, Cardiac/cytology; Myocytes, Cardiac/metabolism; Myocytes, Cardiac/secretion; NIH 3T3 Cells; Nuclear Pore/metabolism; Paracrine Communication/physiology; Stress, Mechanical; Stress, Physiological/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IL33		GO:0005634: nucleus	ECO:0000314:		C		Figure 1A shows IL33 in the nucleus	complete CACAO 11785
HUMAN:IL33		GO:0005737: cytoplasm	ECO:0000314:		C		Figure 1A shows localization of IL33 in the cytoplasm	complete CACAO 11786

References

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