Intestinal adhesions are bands of fibrous tissue that connect the loops of the intestine to each other, to other abdominal organs or to the abdominal wall(1-3). Fibrous tissue formation is regulated by the balance between plasminogen activator inhibitor type 1 ( PAI- 1) and tissue- type plasminogen activator ( tPA), which reciprocally regulate fibrin deposition. Several components of the inflammatory system, including cytokines(4), chemokines, cell adhesion molecules and neuropeptide substance P, have been reported to participate in adhesion formation(4-7). We have used cecal cauterization to develop a unique experimental mouse model of intestinal adhesion. Mice developed severe intestinal adhesion after this treatment. Adhesion development depended upon the interferon-gamma ( IFN-gamma) and signal transducer and activator of transcription- 1 ( STAT1) system. Natural killer T ( NKT) cell - deficient mice developed adhesion poorly, whereas they developed severe adhesion after reconstitution with NKT cells from wild- type mice, suggesting that NKT cell IFN-gamma production is indispensable for adhesion formation. This response does not depend on STAT4, STAT6, interleukin- 12 ( IL- 12), IL- 18, tumor necrosis factor-alpha, Toll- like receptor 4 or myeloid differentiation factor- 88 - mediated signals. Wild- type mice increased the ratio of PAI- 1 to tPA after cecal cauterization, whereas Ifng(-/-) or Stat1(-/-) mice did not, suggesting that IFN-gamma has a crucial role in the differential regulation of PAI- 1 and tPA. Additionally, hepatocyte growth factor, a potent mitogenic factor for hepatocytes(8,9), strongly inhibited intestinal adhesion by diminishing IFN-gamma production, providing a potential new way to prevent postoperative adhesions.
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