title: Human lung fibroblasts inhibit macrophage inflammatory protein-1alpha production by lipopolysaccharide-stimulated macrophages.
abstract: 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.
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan. oshikatu@jichi.ac.jp
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Oshikawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamasawa
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugiyama
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D015232:Dinoprostone