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The aim of this study was to identify differences in Toll-like receptor (TLR) expression patterns in normal and diseased tissues of patients with polyps and colorectal cancer. Eight patients were included in the study group (aged 38 to 72 years). Sixteen HG-U133A oligonucleotide microarrays were analysed including four of colonic polyps, four of adenocarcinoma with different degree of histological differentiation (2 poorly and 2 highly differentiated), and eight of macroscopically normal tissue. The levels of selected TLR mRNA transcripts were analysed. An analysis of all per cent variability values with regard to malignancy stage increasing from polyp to stages I to III adenocarcinoma, and normal colon mucosa shows a statistically significant relationship for TLR2 (increasing) and TLR3 (decreasing). In polyps, copy numbers of TLR3, TLR4 and TLR5 mRNA were the highest and TLR7 mRNA the lowest. In normal colon mucosa of polyposis patients the highest mRNA copy numbers were observed for TLR3, and the lowest for TLR7. TLR3 may serve as a marker of colon tissue metaplasia and may indicate the tendency of normal tissue to form polyps transforming to colorectal cancer.
Autoimmune myocarditis develops after the presentation of heart-specific antigens to autoaggressive CD4+ T cells and after inflammation has infiltrated the tissues. To shed light on global changes in the gene expression of autoimmune myocarditis and to gain further insight into the molecular mechanisms underlying the genesis of myocarditis, we conducted a comprehensive microarray analysis of mRNA using an experimental mouse autoimmune myocarditis model via immunization with α-myosin heavy chain-derived peptides. Of over 39,000 transcripts on a high density oligonucleotide microarray, 466 were under-expressed and 241 over-expressed by ≥ 1.5-fold compared with the controls in BALB/C mouse with autoimmune myocarditis. In this paper, we list the top 50 up-regulated genes related to the immune response. These altered genes encode for leukocyte-specific markers and receptors, the histocompatibility complex, cytokines/receptors, chemokines/receptors, adhesion molecules, components of the complement cascade, and signal transduction-related molecules. Interestingly, matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 were up-regulated, as further revealed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. This indicates that MMPs may act as major regulators of the cytokine profile. Together, these findings provide new insight into the molecular events associated with the mechanism of the autoimmune genesis of myocarditis.
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