Monocyte chemotactic protein 1 upregulates IL-1beta expression in human monocytes.

Monocyte chemotactic protein-1 (MCP-1) chemoattracts and activates monocytes. The nature of the genes that are transcriptionally activated in the monocytes by MCP-1 is not well understood. To identify such genes, human blood monocytes were incubated with or without MCP-1 for periods of 1, 4, and 12 h and the RNA extracted from these monocytes was subjected to differential display. The differentially expressed transcripts were cloned and sequenced. Differential display showed that interleukin-1beta (IL-1beta) gene expression was upregulated by MCP-1 treatment of monocytes for 4 to 12 h. Quantitative PCR and ELISA assays showed that MCP-1 treatment caused elevation in the levels of IL-1beta transcripts and protein, respectively. Immunoblot analysis showed that most of the protein was pro-IL-1beta. Since IL-1beta is known to induce MCP-1 synthesis, the present demonstration that MCP-1 induces IL-1beta synthesis suggests that the induction of each other would amplify the biological effects of these cytokines during inflammation.