Abstract
Annexin 1 is an anti-inflammatory protein that plays a key role in innate immunity by modulating the activation of several types of cells, including neutrophils. Here we have developed a cleavage assay using tagged annexin 1 and observed marked activity in the membrane fraction of activated neutrophils. A combination of inhibitors, transfected cells, and proteomic analyses allowed us to identify proteinase 3 as the main enzyme responsible for this cleavage in the N terminus region of the protein, at least in the context of neutrophil activation. Because annexin 1 is an important endogenous anti-inflammatory mediator, blocking its cleavage by proteinase 3 would augment its homeostatic pro-resolving actions and could represent an opportunity for innovative anti-inflammatory drug discovery.
| Original language | English |
|---|---|
| Pages (from-to) | 29998-30004 |
| Number of pages | 7 |
| Journal | JOURNAL OF BIOLOGICAL CHEMISTRY |
| Volume | 282 |
| Issue number | 41 |
| DOIs | |
| Publication status | Published - 12 Oct 2007 |
Keywords
- Amino Acid Sequence
- Annexin A1
- Anti-Inflammatory Agents
- Cell Line
- Chemistry, Pharmaceutical
- Drug Design
- Epithelial Cells
- Gene Expression Regulation, Enzymologic
- HL-60 Cells
- Humans
- Models, Biological
- Molecular Sequence Data
- Myeloblastin
- Neutrophil Activation
- Neutrophils
- Protein Structure, Tertiary
- Sequence Homology, Amino Acid
- Journal Article
- Research Support, Non-U.S. Gov't