Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease

Pim J Koelink ¹, Saskia A Overbeek , Saskia Braber

⁰Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, , Utrecht, The Netherlands.

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March 26, 2013

View abstract on PubMed

Summary

Proline-glycine-proline (PGP) is elevated in inflammatory bowel disease (IBD) and drives neutrophil inflammation. Neutralizing PGP significantly reduced neutrophil infiltration in IBD models, suggesting a therapeutic target.

Area Of Science

Gastroenterology
Immunology
Biochemistry

Background

Proline-glycine-proline (PGP) is a collagen-derived peptide known to attract neutrophils via CXCR2 in lung diseases.
PGP is generated by matrix metalloproteinases (MMPs) and prolyl endopeptidase (PE).

Purpose Of The Study

To investigate the role and generation of PGP in inflammatory bowel disease (IBD).

Main Methods

Assessed MMP8, MMP9, and PE levels in intestinal tissues from IBD patients and DSS-induced colitis mice.
Measured PGP levels in tissues and ex vivo generated from peripheral blood polymorphonuclear cell (PMN) supernatants.
Utilized PGP neutralization with antagonists and antibodies in DSS-induced colitis models.

Main Results

Elevated MMP8 and MMP9, with normal PE, were found in IBD intestinal tissue.
Increased PGP levels were observed in IBD patients and DSS-treated mice.
PMN supernatants from IBD patients generated more PGP ex vivo.
PGP neutralization significantly reduced neutrophil infiltration in DSS-induced colitis.

Conclusions

The PGP generation pathway is active in the inflamed intestine of IBD patients and in DSS-induced colitis.
PGP plays a crucial role in guiding neutrophil infiltration in IBD, forming a potential vicious cycle of inflammation.

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