Interleukin-1 alpha enhances mast cell growth by a fibroblast-dependent mechanism.
Mast cell hyperplasia is observed in various inflammatory skin diseases. Although the pathogenesis of these conditions remains largely uninvestigated, it has been speculated that lesional mediators provide a favorable microenvironment for mast cell growth. We investigated the effect of an inflammatory cytokine, IL-1 alpha, on mast cell growth in a mast cell/fibroblast coculture system. When mouse bone marrow-derived cultured mast cells (BMMC) were cultured on a NIH/3T3 fibroblast monolayer, IL-1 alpha stimulated mast cell proliferation. However, IL-1 alpha 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 alpha. When BMMC were prepared from W/Wv mice, which lack a 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 alpha was observed. Flow cytometric analysis revealed no enhancement of SCF expression on fibroblasts following stimulation with IL-1 alpha. 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 alpha, and prostaglandin E2 induced mast cell growth in the co-cultures. These results indicate that IL-1 alpha stimulates mast cell growth by a fibroblast-dependent mechanism, in which SCF/c-kit interaction may participate in a major way. The mast cell growth activity induced by this cytokine can, at least in part, be attributed to prostaglandins. Inflammatory cytokines may thus contribute to mast cell hyperplasia in skin diseases.
Kameyoshi
Y
Y
Department of Dermatology, Hiroshima University School of Medicine, Japan. kameyosi@ipc.hiroshima-u.ac.jp
Morita
E
E
Tanaka
T
T
Hiragun
T
T
Yamamoto
S
S
D016475:3T3 Cells; D000818:Animals; D002452:Cell Count; D002455:Cell Division; D018920:Coculture Techniques; D015232:Dinoprostone / Q000494:pharmacology; D006632:Histamine / Q000032:analysis; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D012867:Skin; D019089:Stem Cell Factor / Q000494:pharmacology
D007375:Interleukin-1; D019089:Stem Cell Factor; D006632:Histamine; D015232:Dinoprostone; D007213:Indomethacin