Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion

Lei, Nazi, Franken, Linda, Ruzehaji, Nadira, Offenhaeuser, Carolin, Cowin, Allison J. and Murray, Rachael Z. (2012) Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion. Journal of Cell Science, 125 18: 4288-4296. doi:10.1242/jcs.099507

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ286985_OA.pdf Full text (open access) application/pdf 2.30MB 0

Author Lei, Nazi
Franken, Linda
Ruzehaji, Nadira
Offenhaeuser, Carolin
Cowin, Allison J.
Murray, Rachael Z.
Title Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
Publication date 2012-09-15
Sub-type Article (original research)
DOI 10.1242/jcs.099507
Open Access Status File (Publisher version)
Volume 125
Issue 18
Start page 4288
End page 4296
Total pages 9
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Collection year 2013
Language eng
Abstract Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates Toll-Like Receptor (TLR) signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and lipopolysaccharide (LPS)-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, and wild-type and mutant proteins, we show that Flii is secreted by means of a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine-rich repeat domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii-depleted conditioned medium leads to enhanced macrophage activation and increased TNF secretion compared with cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.
Keyword Flightless
Late endosome
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 09 Dec 2012, 00:46:46 EST by System User on behalf of Institute for Molecular Bioscience