Granulocyte macrophage colony-stimulating factor and interleukin-3 regulate chemokine and chemokine receptor...

The beta-chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha) and its associated receptors are involved in the regulation of pro-inflammatory and haemopoietic processes. This study was designed to investigate regulation of expression MIP-1alpha and its receptors by other haemopoietic cytokines. Murine bone marrow macrophages (BMM) were treated with or without GM-CSF or IL-3 and expression of MIP-1alpha, other chemokines and their receptors examined by Northern blotting. Receptor levels were also examined using Scatchard analysis and functional tests. Treatment of BMM with GM-CSF revealed a striking increase in MIP-1alpha mRNA levels, relative to untreated cells with a corresponding increase in MIP-1alpha protein. A similar increase in mRNA levels was found when BMM were treated with IL-3. An increase in the expression of three other beta-chemokines namely MIP-1beta, MCP-1 and MCP-3, was also found following treatment with GM-CSF or IL-3. We have additionally examined the expression of the known beta-chemokine receptors in BMM and observed an increase in CCR1 mRNA levels following treatment with GM-CSF and IL-3, but no change was seen in the level of CCR5 expression. The increase in CCR1 expression was reflected in an increase in the number of cell surface receptors for MIP-1alpha on the GM-CSF treated BMM and in an enhanced response of the GM-CSF treated BMM to CCR1 ligands. These data suggest that GM-CSF and IL-3 may be involved in mechanisms regulating expression levels of MIP-1alpha and its receptors.