Tissue Proteolysis in Appendicitis with Perforation

• BACKGROUND: Matrix metalloproteinases (MMPs) and serine proteases are able to degrade the extracellular matrix (ECM) and modulate immune responses in the gastrointestinal tract. The purpose of this study was to investigate local proteolysis in perforated appendicitis and its association with the appendix perforation. MATERIALS AND METHODS: Biopsies were taken at the sites of perforation (n = 15) and with a gradually increased distance from it. The expression and distribution of MMP-1, -2, and -9, the tissue inhibitor of metalloproteinases type (TIMP-1), plasminogen activator inhibitor type1 (PAI-1), and urokinase plasminogen activator (uPA) were measured by ELISA. The distribution of MMP-9, TIMP-1, uPA, and PAI-1 in perforated, nonperforated, and uninflamed appendix was investigated by immunohistochemistry with monoclonal antibody technique. RESULTS: MMP-1 expression was highest close to the perforation and was gradually decreased in biopsies in more distal locations (P < 0.01). MMP-9 showed a similar pattern being highest at the sites of perforation (P < 0.05), while MMP-2 expression showed a trend in the opposite direction without statistically significance. The expression of TIMP-1 trended lower at the sites of perforation. PAI-1 was highest at the sites of perforation (P < 0.01) and the uPA expression was similarly elevated close to and at the perforation. CONCLUSIONS: These data indicate a key role of MMP in the pathogenesis of appendix perforation. A local imbalance between MMP-9 and the inhibitor TIMP-1 could potentially contribute to the tissue injury leading to an appendix perforation. The overexpression of PAI-1 at the sites of perforation may also contribute to tissue damage.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Appendicitis

Gastroenterology

Gastroenterologi

Pathology

Patologi

Pathology

Patologi

appendicitis; inflammation; perforation; MMPs; TIMPs; PAI-1; uPA

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)