Recycling endosome-dependent and -independent mechanisms for IL-10 secretion in LPS-activated macrophages.

Abstract:

:IL-10 is a key anti-inflammatory cytokine secreted by activated macrophages as a feedback control mechanism to prevent excessive inflammatory responses. Here, we define multiple intracellular trafficking pathways involved in the secretion of newly synthesized IL-10 from macrophages following TLR4 activation with LPS, and show how this relates to the previously defined trafficking pathways for IL-6 and TNF in macrophages simultaneously producing these proinflammatory cytokines. IL-10 exits the Golgi in multiple tubular carriers, including those dependent on p230GRIP. Some of the IL-10 is then delivered to recycling endosomes, where cytokine sorting may occur prior to its release. Another portion of the IL-10 is delivered to the cell surface in distinct vesicles colabeled for apoE. Thus, we show at least two post-Golgi pathways via which IL-10 is trafficked, ensuring its secretion from activated macrophages under different physiological conditions.

journal_name

J Leukoc Biol

authors

Stanley AC,Lieu ZZ,Wall AA,Venturato J,Khromykh T,Hamilton NA,Gleeson PA,Stow JL

doi

10.1189/jlb.0412191

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

1227-39

issue

6

eissn

0741-5400

issn

1938-3673

pii

jlb.0412191

journal_volume

92

pub_type

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