Recycling endosome-dependent and -independent mechanisms for IL-10 secretion in LPS-activated macrophages
Abstract
Two post-Golgi pathways where IL-10 is trafficked, ensures its secretion from activated macrophages under different physiological conditions. 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.
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The mechanism of IL-10 trafficking and release resembles that of TNF and IL-6.
“The mechanism of IL-10 trafficking and release resembles that of TNF and IL-6 (66).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [66]
IL-10 traffics from Golgi tubular carriers associated with p230/golgin-245 along with TNF-containing vesicles, or in golgin-97-associated tubules.
“IL-10 traffics from Golgi tubular carriers associated with p230/golgin-245 along with TNF-containing vesicles, or in golgin-97-associated tubules.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [66]
The Golgi-associated p110δ isoform of PI3K is a positive regulator of IL-10 release.
“The Golgi-associated p110δ isoform of PI3K was also found to be a positive regulator of IL-10 release.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [66]
Independent of recycling endosomes, IL-10 exits directly from the Golgi to the cell surface in apoE-labeled vesicles.
“Independent of recycling endosomes, IL-10 was also observed to exit directly from the Golgi to the cell surface in apoE-labeled vesicles (66).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [66]
From the Golgi, IL-10-containing vesicles move to recycling endosomes, where VAMP3 and Rab11 modulate transit of IL-10, TNF, and IL-6 to the cell surface.
“From the Golgi, IL-10-containing vesicles move to recycling endosomes, where VAMP3 and Rab11 then modulate the transit of this cytokine – and of TNF and IL-6 – to the cell surface.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [66]
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References 40 · Cited by 55
- Authors
- Stanley, A. C., Lieu, Z. Z., Wall, A. A., Venturato, J., Khromykh, T., Hamilton, N. A., Gleeson, P. A., & Stow, J. L.
- Affiliations
- The University of Queensland (AU)
- The University of Melbourne (AU)
- Corresponding author
- Stow, J L
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-12-01
- Volume
- 92
- Issue
- 6
- Pages
- 1227-1239
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2136621634
- Cited by
- 55
- References
- 40
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 7 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 6 · 2013: 6 · 2012: 1
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council of Australia (#631621)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-10 secretion, macrophages, recycling endosomes, endosomal sorting, post-Golgi trafficking, apolipoprotein E, lipopolysaccharide stimulation, TLR4, anti-inflammatory cytokines, Golgi apparatus, vesicle trafficking
- MeSH terms
- Animals, Cell Membrane, Golgi Apparatus, Lipopolysaccharides, Macrophage Activation, Macrophages, Endosomes, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Interleukin-10, Inflammation Mediators, Protein Transport, RNA Interference, Tumor Necrosis Factors, Mice
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