Down-regulation by IL-4 and up-regulation by IFN-gamma of mast cell induction from mouse spleen cells.
While investigating an involvement of other factors aside from endogenous IL-3 and prostaglandin E (PGE) in mast cell induction from mouse splenocytes, we found that the mast cell induction was inversely proportional to IL-4 levels and tended to directly proportionate IFN-gamma levels in the supernatants recovered on days 2 and 4. Thereafter, we examined the effects of rIFN-gamma, rIL-4, and rIL-10 on mast cell induction. IFN-gamma and IL-10 dose-dependently induced mast cells. Time course study showed an importance of adding rIFN-gamma into the cultures at the early phase (on days 0 and 2 of a 12-day culture). When endogenous IFN-gamma at the early phase was neutralized by anti-IFN-gamma Ab, all stimulants, including rIFN-gamma, rIL-10, and PGE1, failed to induce mast cells. On the contrary, rIL-4 dose-dependently suppressed the mast cell induction by rIFN-gamma, rIL-10, LPS, PGE, and dibutyryl cAMP. The inhibitory effect of IL-4 was observed when IL-4 was added into the cultures at the early phase, but not after day 4. The suppressive action of IL-4 was diminished completely by the addition of neutralizing anti-IL-4 Ab. IL-12, a key regulator of IFN-gamma and IL-4 production, also induced mast cells. These results revealed, for the first time, that IFN-gamma is crucial for the survival and/or differentiation of splenic mast cell precursors and that IL-4 is a key inhibitor for the precursors, although IFN-gamma is not a mast cell growth factor and IL-4 is a growth factor for immature and mature mast cells.
Hu
Z Q
ZQ
Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan.
Zenda
N
N
Shimamura
T
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D015536:Down-Regulation / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects*
D000906:Antibodies; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D003994:Bucladesine; D007371:Interferon-gamma; D007213:Indomethacin