title: 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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: A C
authors.initials: AC
authors.lastname: Stanley
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Lieu
authors.forename: A A
authors.initials: AA
authors.lastname: Wall
authors.forename: J
authors.initials: J
authors.lastname: Venturato
authors.forename: T
authors.initials: T
authors.lastname: Khromykh
authors.forename: N A
authors.initials: NA
authors.lastname: Hamilton
authors.forename: P A
authors.initials: PA
authors.lastname: Gleeson
authors.forename: J L
authors.initials: JL
authors.lastname: Stow
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D034622:RNA Interference; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D016753:Interleukin-10