Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3
Abstract
On human macrophages IL-10 acts as a more potent anti-inflammatory cytokine than IL-6, although both cytokines signal mainly via activation of the transcription factor STAT3. In this study we compare IL-10 and IL-6 signaling in primary human macrophages derived from blood monocytes. Pretreatment of macrophages with PMA or the proinflammatory mediators LPS and TNF-alpha blocks IL-6-induced STAT3 activation, whereas IL-10-induced activation of STAT3 remains largely unaffected. Although LPS induces the feedback inhibitor suppressor of cytokine signaling 3 (SOCS3) in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not depend on gene transcription. We also found that pretreatment of macrophages with IL-10 inhibits subsequent STAT3 activation by IL-6, whereas IL-10-induced STAT3 activation is not affected by preincubation with IL-6. This cross-inhibition is dependent on active transcription and might therefore be explained by different sensitivities of IL-10 and IL-6 signaling toward the feedback inhibitor SOCS3, which is induced by both cytokines. In contrast to the IL-6 signal transducer gp130, which has been previously shown to recruit SOCS3 to one of its phosphotyrosine residues (Y759), peptide precipitation experiments suggest that SOCS3 does not interact with phosphorylated tyrosine motifs of the IL-10R. Taken together, different sensitivities of IL-10 and IL-6 signaling toward mechanisms that inhibit the Janus kinase/STAT pathway define an…
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The signaling of the IL-6 receptor is inhibited by the STAT3-induced protein SOCS3, which does not affect the IL-10 receptor.
“The signaling of the IL-6 receptor is inhibited by the STAT3-induced protein SOCS3, which does not affect the IL-10 receptor (23).”
From Cytokine Response Is Determined by Duration of Receptor and Signal Transducers and Activators of Transcription 3 (STAT3) Activation (2013) · cites this paper as [23]
IL-6 and IL-10 both signal through STAT3 but differ in the architectures of their signaling networks.
“IL-6 and IL-10 both signal through STAT3 but differ in the architectures of their signaling networks.”
From Cytokine Response Is Determined by Duration of Receptor and Signal Transducers and Activators of Transcription 3 (STAT3) Activation (2013) · cites this paper as [23]
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- Authors
- Niemand, C., Nimmesgern, A., Haan, S., Fischer, P., Schaper, F., Rossaint, R., Heinrich, P. C., & Müller-Newen, G.
- Affiliations
- Universitätsklinikum Aachen (DE)
- Institut für Biochemie, Universitätsklinikum RWTH Aachen , Aachen ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-03
- Volume
- 170
- Issue
- 6
- Pages
- 3263-3272
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1740603564
- Cited by
- 357
- References
- 5
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 10 · 2023: 12 · 2022: 15 · 2021: 12 · 2020: 25 · 2019: 19 · 2018: 26 · 2017: 18 · 2016: 23 · 2015: 16 · 2014: 24 · 2013: 22 · 2012: 15
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT3 activation, IL-6 signaling, IL-10 signaling, SOCS3, macrophages, gp130, IL-10 receptor, product inhibition, anti-inflammatory cytokines, LPS, TNF-α, PMA, transcriptional regulation
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Interleukin-6 Inhibitors, Anti-Inflammatory Agents, Non-Steroidal, Cells, Cultured, DNA-Binding Proteins, Enzyme Activation, Enzyme Inhibitors, Humans, Lipopolysaccharides, Macrophages, Proteins, Repressor Proteins, Tetradecanoylphorbol Acetate, Transcription Factors, Protein Biosynthesis, Tumor Necrosis Factor-alpha, Signal Transduction, Trans-Activators, Interleukin-6, Interleukin-10, Protein Tyrosine Phosphatases, Inflammation Mediators, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Feedback, Physiological, Intracellular Signaling Peptides and Proteins, Mitogen-Activated Protein Kinase 3, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 11
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