インターロイキン1αは線維芽細胞依存的にマスト細胞の増殖を促進する

Mast cell hyperplasia is observed in variousinflammatory skin diseases. Although the pathogenesis of these conditions remains largely uninvestigated, it is speculated that lesional mediators provide favorable microenvironment for mast cell growth. We have investigated the effect of an inflammatory cytokine, IL-1, on mast cell growth in a mast cell/fibroblast co-culture system. When mouse bone marrow-derived cultured mast cells (BMMC) were cultured on a NIH/3T3 fibroblast monolayer, IL-1 stimulated mast cell proliferation. However, IL-1did not stimulate 3H-thymidine incorporation in BMMC in the absence of fibroblasts. Separation of BMMC from fibroblasts by a permeable micropore membrane reduced the effect of IL-1. When BMMC were prepared from W/Wv-mice, which lack functional c-kit, or when NIH/3T3 fibroblasts were substituted with Sl/Sld-derived fibroblasts, which lack membrane-bound stem cell factor (SCF), a lower, but significant, effect of IL-1 was observed. Flow cytometric analysis revealed no enhancement of SCF expression on fibroblasts by IL-1. Neutralizing antibodies against IL-3, IL-4, IL-10, and nerve growth factor (NGF) showed no inhibition. On the other hand, indomethacin inhibited the effect of IL-1, and prostaglandin E2 induced mast cell growth in the co-culture. These results indicate that IL-1 stimulates mast cell growth by a fibroblast-dependent mechanism, where SCF/c-kit interaction may participate in a major way. The mast cell growth activity induced by this cytokine is, at least in part, attributed to prostaglandins. Inflammatory cytokines may thus contribute to mast cell hyperplasia in skin diseases.広島大学(Hiroshima University)博士(医学)Medicinedoctora