IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcepsilonRI signals.
The IL-1-related molecules, IL-1 and IL-18, can promote Th2 cytokine production by IgE/antigen-FcepsilonRI-stimulated mouse mast cells. Another IL-1-related molecule, IL-33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL-33 on mast cell function are poorly understood. We found that IL-33, but not IL-1beta or IL-18, induced IL-13 and IL-6 production by mouse bone marrow-derived, cultured mast cells (BMCMCs) independently of IgE. In BMCMCs incubated with the potently cytokinergic SPE-7 IgE without specific antigen, IL-33, IL-1beta, and IL-18 each promoted IL-13 and IL-6 production, but the effects of IL-33 were more potent than those of IL-1beta or IL-18. IL-33 promoted cytokine production via a MyD88-dependent but Toll/IL-1R domain-containing adaptor-inducing IFN-beta-independent pathway. By contrast, IL-33 neither induced nor enhanced mast cell degranulation. At 200 ng/ml, IL-33 prolonged mast cell survival in the absence of IgE and impaired survival in the presence of SPE-7 IgE, whereas at 100 ng/ml, IL-33 had no effect on mast cell survival in the absence of IgE and reduced mast cell survival in the presence of IgE. These observations suggest potential roles for IL-33 in mast cell- and Th2 cytokine-associated immune responses and disorders.
Ho
Lien H
LH
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.
Ohno
Tatsukuni
T
Oboki
Keisuke
K
Kajiwara
Naoki
N
Suto
Hajime
H
Iikura
Motoyasu
M
Okayama
Yoshimichi
Y
Akira
Shizuo
S
Saito
Hirohisa
H
Galli
Stephen J
SJ
Nakae
Susumu
S
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D015550:Cell Degranulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007073:Immunoglobulin E / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis*; D053727:Interleukin-18 Receptor alpha Subunit / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017455:Receptors, IgE / Q000276:immunology*; D053573:Receptors, Interleukin-1 Type I / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects*
D033942:Adaptor Proteins, Vesicular Transport; D007073:Immunoglobulin E; D018793:Interleukin-13; D053727:Interleukin-18 Receptor alpha Subunit; D000067596:Interleukin-33; D007378:Interleukins; D020928:Mitogen-Activated Protein Kinases; D053594:Myeloid Differentiation Factor 88; D017455:Receptors, IgE; D053573:Receptors, Interleukin-1 Type I; C508573:Il18r1 protein, mouse; C506535:Il33 protein, mouse; C476286:Ticam1 protein, mouse