Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease
| Autor: | Pim J. Koelink, Simone C. Wolfkamp, Gert Folkerts, Aletta D. Kraneveld, John A. W. Kruijtzer, Johan Garssen, J. Edwin Blalock, Rolf W. Sparidans, Saskia A. Overbeek, Mary E. Morgan, Hein W. Verspaget, Caleb Jones, Mojtaba Abdul Roda, Anje A. te Velde, Paul A.J. Henricks, Patricia L. Jackson, Saskia Braber |
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| Přispěvatelé: | Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Gastroenterology and Hepatology |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Adolescent endocrine system diseases Matrix metalloproteinase MMP9 Biology MMP8 Inflammatory bowel disease 03 medical and health sciences Mice Young Adult 0302 clinical medicine medicine polycyclic compounds Animals Humans Colitis Intestinal Mucosa Child 030304 developmental biology Aged 0303 health sciences integumentary system Inflammatory Bowel Disease Serine Endopeptidases Gastroenterology Middle Aged medicine.disease Inflammatory Bowel Diseases digestive system diseases 3. Good health Intestines Mice Inbred C57BL carbohydrates (lipids) Disease Models Animal Matrix Metalloproteinase 8 Matrix Metalloproteinase 9 Neutrophil Infiltration 030220 oncology & carcinogenesis Immunology Immunohistochemistry Female Collagen Prolyl Oligopeptidases Infiltration (medical) Ex vivo |
| Zdroj: | Gut, 63(4), 578-587. BMJ Publishing Group Gut |
| ISSN: | 0017-5749 |
| Popis: | Objective Proline–glycine–proline (PGP) has been shown to have chemotactic effects on neutrophils via CXCR2 in several lung diseases. PGP is derived from collagen by the combined action of matrix metalloproteinase (MMP) 8 and/or MMP9 and prolyl endopeptidase (PE). We investigated the role of PGP in inflammatory bowel disease (IBD). Design In intestinal tissue from patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis, MMP8, MMP9 and PE were evaluated by ELISA, immunoblot and immunohistochemistry. Peripheral blood polymorphonuclear cell (PMN) supernatants were also analysed accordingly and incubated with collagen to assess PGP generation ex vivo. PGP levels were measured by mass spectrometry, and PGP neutralisation was achieved with a PGP antagonist and PGP antibodies. Results In the intestine of patients with IBD, MMP8 and MMP9 levels were elevated, while PE was expressed at similar levels to control tissue. PGP levels were increased in intestinal tissue of patients with IBD. Similar results were obtained in intestine from DSS-treated mice. PMN supernatants from patients with IBD were far more capable of generating PGP from collagen ex vivo than healthy controls. Furthermore, PGP neutralisation during DSS-induced colitis led to a significant reduction in neutrophil infiltration in the intestine. Conclusions The proteolytic cascade that generates PGP from collagen, as well as the tripeptide itself, is present in the intestine of patients with IBD and mice with DSS-induced colitis. PGP neutralisation in DSS-treated mice showed the importance of PGP-guided neutrophilic infiltration in the intestine and indicates a vicious circle in neutrophilic inflammation in IBD. |
| Databáze: | OpenAIRE |
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