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Osteoprotegerin exerts its pro-inflammatory effects through nuclear factor-κB activation
Lily Nahidi1, Steven T Leach, Daniel A Lemberg
1School of Women's and Children's Health, University of New South Wales, High Street, Randwick, Sydney, NSW, 2031, Australia, Lily.Nahidi@sesiahs.health.nsw.gov.au.
Digestive Diseases and Sciences
|September 20, 2013
Summary
Osteoprotegerin (OPG) triggers gut barrier dysfunction and inflammation by activating NF-κB, suggesting a role in inflammatory bowel disease (IBD) pathogenesis.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Osteoprotegerin (OPG) is a TNF receptor superfamily member that inhibits osteoclast activity.
- OPG is a potential disease marker for inflammatory bowel disease (IBD).
- The role of OPG in intestinal epithelial inflammation is not well understood.
Purpose of the Study:
- To investigate the role of OPG in intestinal inflammation.
- To explore the potential role of OPG in IBD pathogenesis.
Main Methods:
- In vitro co-culture of Caco-2 and HT-29 cells with TNF-α or OPG.
- Measurement of IL-8 protein and mRNA levels.
- Assessment of intestinal barrier integrity and function using Ussing chamber, western blotting, real-time PCR, and immunofluorescence.
Main Results:
- OPG treatment increased monolayer permeability and diminished tight junction integrity, similar to TNF-α.
- OPG elevated IL-8 protein and gene expression.
- OPG induced NF-κB activation, evidenced by inhibition of NF-κB kinase subunit-α phosphorylation.
Conclusions:
- OPG exhibits pro-inflammatory properties by inducing gut barrier dysfunction.
- OPG promotes the secretion of pro-inflammatory cytokines.
- OPG may contribute to IBD pathogenesis via NF-κB activation.
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