IL-10 differentially regulates mRNA expression induced by lipopolysaccharide and interferons in murine peritoneal macrophages

Abstract

IL-10 has been referred to as 'macrophage deactivator' because it suppresses macrophage activity by blocking cytokine production and accessory functions. The purpose of this study was to compare the effects of IL-10 on genes that are induced by the well characterized macrophage activators, lipopolysaccharide (LPS) and interferons (IFNs). Using Northern blot analysis to measure the effects of IL-10 on the expression of a large panel of LPS and IFNinducible genes, the data suggest that in murine macrophages IL-10 is not a general suppressor of gene induction but, rather, exerts differential effects on gene expression. Induction of certain genes by LPS was indeed blocked to a great extent (70-80%), while expression of others were less inhibited, not modulated at all, or augmented by IL-10. IFN-α and IFN-γ induce a subset of the genes that are also induced by LPS and, within this subset, IL-10 was found to interfere to a lesser extent with IFN- than LPS-induced gene expression. The participation of NF-KB in the induction of IL-10 inhibitable genes and shared common elements in IFN and IL-10 signaling pathways are discussed as potential explanations for these observations.

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