Glucocorticoid suppresses autocrine survival of mast cells by inhibiting IL-4 production and ICAM-1 expression.
When mast cells are activated through their high affinity IgE receptors (FcepsilonRI), release of chemical mediators is followed by secretion of multiple cytokines. In this work, we report that IL-3-dependent mast cell line MC9 undergoes apoptosis when IL-3 is withdrawn. However, cross-linking of FcepsilonRI prevents apoptosis of MC9 by an autocrine mechanism, producing IL-3, IL-4, and GM-CSF. Although stimulated MC9 synthesizes mRNAs and proteins of these cytokines, secretion of endogenous IL-3 and GM-CSF is not enough for cell survival, whereas IL-4 itself does not have survival effect on MC9, but it induces cell aggregation by expressing LFA-1 and makes it reactive to endogenous growth factors. Addition of dexamethazone (DXM) to MC9 results in significant down-regulation of IL-4 mRNA in activated MC9. However, mRNA levels of IL-3 and GM-CSF are not changed by DXM. DXM also directly down-regulates the expression of ICAM-1 that is the high affinity ligand of LFA-1, by which the self-aggregation of MC9 is inhibited. Thus, glucocorticoids suppress autocrine survival of mast cells by inhibiting IL-4 production and ICAM-1 expression.
Yoshikawa
H
H
Department of Parasitology and Immunology, Yamanashi Medical University, Tamaho-cho, Yamanashi, Japan.
Nakajima
Y
Y
Tasaka
K
K
D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D002470:Cell Survival; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007152:Immunologic Capping; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007377:Interleukin-3 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D017455:Receptors, IgE / Q000378:metabolism
D005938:Glucocorticoids; D007377:Interleukin-3; D016169:Lymphocyte Function-Associated Antigen-1; D017455:Receptors, IgE; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor