Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2005; 11(40): 6312-6321
Published online Oct 28, 2005. doi: 10.3748/wjg.v11.i40.6312
Expression of matrix metalloproteinases and tissue inhibitor metalloproteinases increases in X-irradiated rat ileum despite the disappearance of CD8a T cells
Carine Strup-Perrot, Marie-Catherine Vozenin-Brotons, Marie Vandamme, Christine Linard, Denis Mathé
Carine Strup-Perrot, Marie-Catherine Vozenin-Brotons, Marie Vandamme, Christine Linard, Laboratoire d’étude des pathologies Radio-induites, SRBE/DRPH, Institut de Radioprotection et de Sûeté Nucléire, Fontenay-aux-Roses 92262, France
Marie-Catherine Vozenin-Brotons, Denis Mathé, Laboratoire UPRES EA 27-10 ‘Radiosensibilité des tumeurs et tissus sains’, Institut Gustave Roussy/Institut de Radioprotection et de Sûeté Nucléire, Villejuif Cedex 94805, France
Author contributions: All authors contributed equally to the work.
Correspondence to: Carine Strup-Perrot, Laboratoire d’étude des pathologies Radio-induites, SRBE/DRPH, Institut de Radioprotection et de Sûeté Nucléaire, Fontenay-aux-Roses 92262, France. carine.strup@irsn.fr
Telephone: +33-1-58357760
Received: October 12, 2004
Revised: December 21, 2004
Accepted: December 23, 2004
Published online: October 28, 2005
Abstract

AIM: To investigate their expression and activity in the rat ileum after exposure to ionizing radiation along with that of the cellular effectors and molecular mediators involved in the regulation of MMPs.

METHODS: Rats were exposed to a single 10-Gy dose of X-rays delivered to the abdomen. A combination of methods, such as zymography, immunohistochemistry and real time reverse transcriptase-polymerase chain reaction, were used to localize and quantify MMPs and the molecules involved in MMP activating and inhibitory pathways (plasmin/plasminogen, TIMPs), CD8+, as well as inflammatory (interleukin (IL)-1β, IL-8, tumor necrosis factor-α, TNF-α) and fibrogenic mediators (transforming growth factor-β1-3) within ileal tissue at 1, 3, and 7 d after irradiation.

RESULTS: A marked increase in MMP-2 and -14 mRNA and protein levels associated with an increased activity of MMP-2 was observed in irradiated ileal tissue. MMP-2 and -14 expression was mainly observed in inflammatory, epithelial, and mesenchymal cells, whereas a slight increase in MMP-3 expression was detected in the few infiltrating macrophages at d 1 after irradiation. Conversely, MMP-1, -7, and -9 mRNA levels were not found to be affected by abdominal irradiation. Irradiation was found to induce disappearance of CD8+ cells. Furthermore, we have observed that TNF-α and IL-1β protein levels increased 6 h after irradiation, whereas those of IL-8 only increased after 3 d and was concomitant with neutrophil infiltration. In addition, the expressions of molecules involved in MMP activating and inhibitory pathways (urokinase-type plasminogen activator and tissue-type plasminogen activator; TIMP-1, TIMP-2, and plasminogen activator-inhibitor-1) were found to be increased after abdominal irradiation.

CONCLUSION: This study showed that abdominal irradiation induces an acute remodeling of the ileum associated with an increased expression of MMPs and TIMPs that do not involve CD8+ T cells but involve mesenchymal and epithelial cells, although to a lesser extent, and probably even soluble inflammatory and fibrogenic mediators.

Keywords: Matrix metalloproteinases; Irradiation; Ileum; T cells; Cytokines