Premium
The Dynamics and Mechanisms of Interleukin‐1α and β Nuclear Import
Author(s) -
Luheshi Nadia M.,
Rothwell Nancy J.,
Brough David
Publication year - 2009
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2008.00840.x
Subject(s) - biology , microbiology and biotechnology , nuclear transport , nuclear protein , microglia , inflammation , cytokine , cytosol , fluorescence recovery after photobleaching , innate immune system , cell nucleus , interleukin 15 , secretion , immune system , interleukin , immunology , nucleus , transcription factor , genetics , gene , biochemistry , membrane , enzyme
Pro‐inflammatory members of the interleukin‐1 (IL‐1) family of cytokines (IL‐1α and β) are important mediators of host defense responses to infection but can also exacerbate the damaging inflammation that contributes to major human diseases. IL‐1α and β are produced by cells of the innate immune system, such as macrophages, and act largely after their secretion by binding to the type I IL‐1 receptor on responsive cells. There is evidence that IL‐1α is also a nuclear protein that can act intracellularly. In this study, we report that both IL‐1α and IL‐1β produced by microglia (central nervous system macrophages) in response to an inflammatory challenge are distributed between the cytosol and the nucleus. Using IL‐1‐β‐galactosidase and IL‐1‐green fluorescent protein chimeras (analyzed by fluorescence recovery after photobleaching), we demonstrate that nuclear import of IL‐1α is exclusively active, requiring a nuclear localization sequence and Ran, while IL‐1β nuclear import is entirely passive. These data provide valuable insights into the dynamic regulation of intracellular cytokine trafficking.