IL-4 inhibits the LPS-induced expression of CD14 and monocyte-specific esterase mRNA in MONO-MAC-6 cells

The human MONO-MAC-6 cell line expresses the monocyte-associated differentiation markers CD14 and monocyte-specific esterase (MSE) and can be stimulated by lipopolysaccharide (LPS) to produce high mRNA levels of monocyte-related cytokines. This similarity to human peripheral blood monocytes (PBMo) renders this cell line a promising model for studies of monocyte activation and differentiation. Interleukin-4 (IL-4) is known to act antagonistically to LPS during the activation process of PBMo, inhibiting the production of cytokines. Therefore, this study was designed to compare the effects of IL-4 and LPS on the expression of monocytic markers and tumor necrosis factor alpha (TNF alpha) mRNA on PBMo and the MONO-MAC-6 cell line. IL-4 inhibited the LPS-induced expression of TNF alpha mRNA in PBMo and downregulated the LPS receptor CD14 but it had no influence on MONO-MAC-6 cells regarding these parameters. However, upregulation of CD14 and MSE mRNA expression in the cell line by a 2-day incubation with LPS were inhibited by IL-4. This response to IL-4 after long-term treatment with LPS was seemingly contradictory to the missing reduction of TNF alpha mRNA expression after short-term incubation with LPS. Obviously long-term treatment with LPS made the cells responsive to IL-4. The increase in responsiveness was not due to IL-4 receptor (IL-4R) upregulation, as LPS did not influence the constitutive expression of the IL-4R.