Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion.
Lei, Nazi, Franken, Linda, Ruzehaji, Nadira, Offenhauser, Caroli, Cowin, Allison, & Murray, Rachael Zoe (2012) Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion. Journal of Cell Science, 125(18), pp. 4288-4296.
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 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 LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) 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 media leads to enhanced macrophage activation and increased TNF secretion compared to 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.
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|Item Type:||Journal Article|
|Keywords:||Tissue Repair, Wound Healing, Inflammation|
|ISSN:||1477-9137 (online) 0021-9533 (print)|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2013 The Company of Biologists Ltd.|
|Copyright Statement:||author can archive pre-print (ie pre-refereeing)|
|Deposited On:||11 Jan 2013 03:32|
|Last Modified:||25 Oct 2016 23:41|
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