Discovery and Analysis of Inflammatory Disease-Related Genes Using cDNA Microarrays

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 6; pp. 2150 - 2155
• Main Authors: Heller, Renu A., Schena, Mark, Chai, Andrew, Shalon, Dari, Bedilion, Tod, Gilmore, James, Woolley, David E., Davis, Ronald W.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 18.03.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Arthritis; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Biochemistry; Biological Sciences; Cartilage - immunology; Cartilage - metabolism; Cell Line; Cell lines; Cells, Cultured; Chemokines; Chondrocytes; Complementary DNA; Connective tissues; Cytokines; Cytokines - biosynthesis; Cytokines - genetics; Deoxyribonucleic acid; DNA; DNA, Complementary; Genes; Genetic Techniques; Humans; Inflammation - genetics; Inflammation - immunology; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - immunology; Macrophages - immunology; Macrophages - metabolism; Messenger RNA; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - genetics; Pathology; Synovial Membrane - immunology; Synovial Membrane - metabolism; T lymphocytes; Tissue samples
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.6.2150

cDNA microarray technology is used to profile complex diseases and discover novel disease-related genes. In inflammatory disease such as rheumatoid arthritis, expression patterns of diverse cell types contribute to the pathology. We have monitored gene expression in this disease state with a microarray of selected human genes of probable significance in inflammation as well as with genes expressed in peripheral human blood cells. Messenger RNA from cultured macrophages, chondrocyte cell lines, primary chondrocytes, and synoviocytes provided expression profiles for the selected cytokines, chemokines, DNA binding proteins, and matrix-degrading metalloproteinases. Comparisons between tissue samples of rheumatoid arthritis and inflammatory bowel disease verified the involvement of many genes and revealed novel participation of the cytokine interleukin 3, chemokine Groα and the metalloproteinase matrix metallo-elastase in both diseases. From the peripheral blood library, tissue inhibitor of metalloproteinase 1, ferritin light chain, and manganese superoxide dismutase genes were identified as expressed differentially in rheumatoid arthritis compared with inflammatory bowel disease. These results successfully demonstrate the use of the cDNA microarray system as a general approach for dissecting human diseases.