Abstract
Background: 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.
Highlights
Conflicting data describe Interleukin 33 as a nuclear factor and ligand for a transmembrane receptor complex
Because Interleukin 33 (IL-33) is a 32 kilodalton protein, fusion to a fluoroprotein roughly doubles its molecular weight; it is possible that our current understanding of IL-33 behavior is biased by an artificial restriction of cellular mobility induced by fluoroprotein fusion
We describe IL-33 as a multi-organelle protein released from mechanically stressed cells
Summary
Conflicting data describe Interleukin 33 as a nuclear factor and ligand for a transmembrane receptor complex. 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. An alterative hypothesis to resolve this inconsistency is that IL-33 is trafficked for release from living cells via non-classical mechanisms upon sublethal biomechanical strain To address this possibility, we sought to clarify the subcellular location and inter-organelle flux of IL-33 in resting and mechanically stimulated cells, and explored IL-33 release both in vitro and in vivo
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
