Local expression of fractalkine and macrophage-related matrix metalloproteinases in patiets with inflammatory bowel diseases: Regulation of inflammation and distinguishing features in Crohn’s disease and ulcerative colitits *
Inflammatory bowel diseases（IBD）, such as ulcerative colitis（UC）and Crohn's disease（CD）, are relapsing chronic inflammatory disorders of the gut of unknown origin. Fractalkine（FKN）is a unique chemokine that is well known to induce the recruitment and accumulation of monocytes in inflamed tissue. However, it remains unclear whether FKN is involved in the local inflammation in IBD. The aims of this study were to assess the pathognomonic roles of monocyte/macrophage-related chemokines such as FKN and matrix metalloproteinases（MMPs）in IBD, to determine what the possible mechanisms regulating the local inflammation in these conditions are, and to investigate the distinguishing features of the local expression of such chemokines and macrophage-related MMPs in UC and CD. Twenty patients with UC（14 in the active phase, 6 quiescent）, 10 patients with active CD and 10 healthy subjects were enrolled in this study. During colonoscopy, some biopsy samples were taken from the ileum, appendiceal orifice, sigmoid colon, and rectum. Immunohistochemistry and the reverse transcription polymerase chain reaction were used to determine the expression of FKN, monocyte chemoattractant protein-1（MCP-1）, MMP-3，-9，and-12 in these samples. In the noninflamed mucosa of the patients with quiescent UC, neither the number of immunohistochemically positive cells for chemokines and MMPs or expression of the mRNA of such substances increased, as expected. In patients with active UC and active CD, both mRNA expression and the number of immunohistochemically positive cells significantly increased in endoscopically inflamed mucosa. In endoscopically noninflamed mucosa in patients with active IBD, there was a discrepancy between the immunohistochemical findings and mRNA expression;that is, the mRNA expression of chemokines and MMPs was strikingly accelerated despite the absence of any increase in immunohistochemically positive cells. In the terminal ileum, FKN, MMP-3，-9，and -12 were strongly expressed even in the noninflamed mucosa in active CD but not in active UC. In contrast, in the appendiceal orifice, MCP-1, MMP-3, and -9 were strongly expressed even in the noninflamed mucosa in active UC as compared with their expression in active CD. In noninflamed mucosa in active IBD, the protein expression of chemokines and macrophage-related MMPs was not accelerated despite a striking increase in mRNA expression. This finding suggests a pivotal role of post-transcriptional regulation in controlling the local inflammation in IBD. Therefore, assessment of the local status of chemokines and macrophage-related MMPs expression in the terminal ileum and appendiceal orifice may become an alternative for making a correct diagnosis in patients with indeterminate colitis. （Accepted on October 27，2004）
