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Protein kinase C mediates experimental colitis in the rat
J F Brown1, Q Chang, B D Soper
1Department of Physiology, Faculty of Medicine, University of Western Ontario, London, Ontario, Canada N6A 5C1.
The American Journal of Physiology
|March 10, 1999
Summary
Increases in Protein Kinase C (PKC) activity are a key factor in causing colitis. Blocking PKC reduces colitis symptoms, suggesting PKC is a direct mediator of this inflammatory disease.
Area of Science:
- Gastroenterology
- Cell Biology
- Immunology
Background:
- Protein Kinase C (PKC) is crucial for cell signaling in physiological processes.
- Elevated PKC activity is linked to inflammatory conditions like ulcerative colitis.
Purpose of the Study:
- To investigate the role of PKC as a causative mediator in the initiation of experimentally induced colitis in rats.
Main Methods:
- Colitis was induced using 2,4,6-trinitrobenzenesulfonic acid (TNBS) or phorbol 12-myristate 13-acetate (PMA).
- Assessed mucosal damage, neutrophil infiltration, PKC activity, and PKC isoform protein content.
- PKC antagonists (staurosporine, GF-109203X) and neutropenia were used to evaluate PKC's role.
Main Results:
- TNBS treatment significantly increased PKC activity and mucosal injury within 4 hours.
- PKC isoforms beta, delta, and epsilon increased, while alpha decreased post-TNBS.
- PKC antagonists reduced TNBS-induced PKC activity and mucosal damage.
- PMA-induced PKC activation also caused mucosal damage, inhibited by antagonists.
- Neutrophil infiltration was not essential for TNBS-induced injury or PKC activity.
Conclusions:
- Increased PKC activity plays a causative role in TNBS-induced colitis.
- The PKC-mediated inflammatory response in colitis does not appear to involve neutrophils.