| Interleukin 33 as a mechanically responsive cytokine secreted by living cells. | |
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MedLine Citation:
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PMID: 22215666 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 its basic biology 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. A complete and precise description of IL-33 behavior is therefore lacking. We determined the sub-cellular 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 culture and in vivo, mechanical strain induced IL-33 secretion in the absence of necrosis. These data document IL-33s dynamic inter-oganelle trafficking and release during biomechanical overload. As such we recharacterize IL-33 as a both and inflammatory as well as mechanically responsive cytokine secreted by living cells. |
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Authors:
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Rahul Kakkar; Hillary Hei; Stephan Dobner; Richard T Lee |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-3 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Massachusetts General Hospital, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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