Effects of interleukin-1beta, interleukin-13 and transforming growth factor-beta on gene expression in human airway...

Inflammatory gene expression in airway smooth muscle may be influenced by its inflammatory milieu. We analysed the gene expression profile of airway smooth muscle cells cultured from human airways exposed to a pro-inflammatory cytokine, interleukin-1beta, a T helper-2 cytokine, interleukin-13, and to a growth factor, transforming growth factor (TGF)beta1 (10 ng/ml each) after 4 and 24 h using the Affymetrix GeneChip 95A array which detects approximately 12,500 genes and expression sequence tags (ESTs). Airway smooth muscle cells were responsive to each cytokine with distinctive patterns of gene expression for cytokines, chemokines, adhesion and signalling proteins, and transcription factors. Interleukin-1beta induced the highest number of genes such as cytokines/chemokines including interleukin-8, growth-related oncogene (GRO)-alpha, -beta and -gamma, epithelial neutrophil activating protein (ENA)-78, monocyte chemotactic protein (MCP)-1, -2 and -3 and eotaxin. Using quantitative real-time reverse transcription-polymerase chain reaction, the expression of GRO-alpha, -beta and -gamma, interleukin-8 and eotaxin by interleukin-1beta was confirmed, with good correlation with microarray data. Transforming growth factor (TGF)beta1 induced other growth factors such as connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), insulin growth factor (IGF) and many structural and extracellular matrix proteins. Interleukin-13 was the weakest inducer, with stimulation of eotaxin and genes of unknown function. While many genes were co-regulated at 4 and 24 h, there were also differences in expression patterns. Interleukin-1beta induces a predominantly pro-inflammatory profile while TGFbeta1 can be linked to proliferative and matrix changes. The rich profile of mediators, growth factors and signalling molecules released from airway smooth muscle depends on the inflammatory milieu.