Human lung fibroblasts inhibit macrophage inflammatory protein-1alpha production by lipopolysaccharide-stimulated macrophages

We investigated the effect of interaction between lung fibroblasts and macrophages on macrophage inflammatory protein 1alpha (MIP-1alpha) production by macrophages. In a co-culture system consisting of WI-38 lung fibroblasts layered over THP-1 macrophages stimulated with lipopolysaccharide (LPS), MIP-1alpha production by THP-1 was significantly lower in co-culture with WI-38 than in THP-1 alone. Treatment with conditioned medium generated from WI-38 (CM-WI-38) suppressed MIP-1alpha production and mRNA expression in THP-1 cells. Such inhibitory effect of CM-WI-38 on MIP-1alpha production was abrogated by treatment with indomethacin, NS-398 (a specific COX-2 inhibitor), or anti-prostaglandin E(2) antibody. Furthermore, even in a transwell filter system separating both types of cells, co-culture-induced reduction of MIP-1alpha production was observed. Therefore, soluble factors such as prostaglandin E(2) released from lung fibroblasts are responsible for the co-culture-induced inhibition of macrophage-derived MIP-1alpha production, suggesting that immune and inflammatory cell interactions can contribute to the modulatory mechanisms involved in the regulation of the inflammatory or fibrotic process.