Identification of differentially expressed genes regulated by Interleukin-1beta in normal human tracheobronchial epithelial cells using oligonucleotide microarray

Proc Amer Assoc Cancer Res, Volume 45, 2004 4685 Interleukin-1beta (IL-1beta) is a pleiotropic proinflammatory cytokine involved in lung inflammation. We have shown that IL-1beta induced mucus hypersecretion in cultured normal human tracheobronchial epithelial (NHTBE) cells. Recently, it also has been demonstrated that IL-1beta was involved in tumor invasiveness and angiogenesis. To determine the genes or pathways regulated by IL-1beta, we performed oligonucleotide microarray analysis using total RNA isolated from NHTBE cells after treatment with IL-1beta (2.5 ng/ml) for 8 hr. Microarray analysis using Affymetrix Genechip, U133A, revealed that 52 genes were upregulated and 2 genes were down regulated by more than three folds (lower bound of 90% confidence interval) in IL-1beta treated cells compared to the untreated cells. The substantially upregulated genes include chemokines, such as C-C-motif ligand 20 (CCL20), C-X-C-motif ligand (CXCL) 2, CXCL3, CXCL5, and CXCL6. Cyclooxygenase-2 and matrix metalloproteinase 12 were also significantly upregulated by IL-1beta. These genes were known to be involved in inflammation and metastasis. Besides, anti-apoptotic genes such as BCL2A1, TNF5, and NF-kappaB were found upregulated. Our results indicated that the effects of IL-1beta on inflammation and metastasis might be mediated mainly through upregulation of these chemokines and inhibit apoptosis in NHTBE cells via upregulation of BCL2A1, TNF5, and NF-kappaB. This work was supported in part by NIEHS and Eli Lilly Company.