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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
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IL-6 trans-signaling is another pathway to upregulate Osteopontin
Takaaki Uchibori1, Kazuyuki Matsuda1, Takahiro Shimodaira1
1Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan.
Cytokine
|November 19, 2016
Summary
Interleukin-6 (IL-6) trans-signaling, triggered by IL-1β, upregulates osteopontin (OPN) in macrophages. Inhibiting IL-6 trans-signaling pathways reduces OPN levels, suggesting a therapeutic target for fibrotic conditions.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Osteopontin (OPN) is a pro-fibrotic cytokine.
- Interleukin-6 (IL-6) signaling occurs via classic or trans-signaling pathways.
- IL-6 trans-signaling involves soluble IL-6 receptor (sIL-6R).
Purpose of the Study:
- To investigate the role of IL-6 trans-signaling in osteopontin (OPN) upregulation.
- To determine the effect of IL-1β stimulation on OPN, IL-6, sIL-6R, and ADAM17 expression.
- To evaluate the inhibitory effects of specific pathway inhibitors on OPN upregulation.
Main Methods:
- THP-1 cells and macrophages were stimulated with IL-1β.
- Expression of OPN, IL-6, sIL-6R, and ADAM17 was quantified.
- Inhibitors targeting IL-6, sIL-6R, ADAM17, and IL-6 trans-signaling were used.
Main Results:
- IL-1β stimulation upregulated OPN and induced IL-6 production in macrophages.
- Inhibitors of IL-6, IL-6 receptor (IL-6R), and IL-6 trans-signaling (sgp130) attenuated OPN upregulation.
- ADAM17 inhibition also significantly reduced IL-1β-induced OPN increase.
Conclusions:
- IL-1β induces IL-6 and sIL-6R, potentially activating IL-6 trans-signaling.
- IL-6 trans-signaling contributes to osteopontin upregulation in macrophages.
- Macrophages are a source of IL-6 and sIL-6R, driving IL-6 trans-signaling.
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