title: IgE signaling suppresses FcepsilonRIbeta expression.
abstract: Activation of the high-affinity receptor for IgE, FcepsilonRI, is known to elicit its rapid down-regulation through internalization and degradation. In keeping with this, expression of all three FcepsilonRI subunits is decreased at the protein level after cross-linkage of IgE with antigen. However, we find that the FcepsilonRI beta-subunit is also selectively suppressed at the mRNA level, through a pathway primarily involving Fyn, Syk, PI3K, and NF-kappaB. IgG or calcium ionophore, stimuli known to mimic portions of the IgE signaling cascade, similarly suppressed beta-subunit expression. LPS, a NF-kappaB-activating TLR ligand, did not alter beta-subunit expression. As IgE increases FcepsilonRI expression, we examined the coordinated regulation of FcepsilonRI subunits during culture with IgE, followed by cross-linkage with antigen. IgE increased the expression of all three FcepsilonRI subunits and strikingly induced expression of the antagonistic beta(T). The ratio of beta:beta(T) protein expression decreased significantly during culture with IgE and was reset to starting levels by antigen cross-linkage. These changes in protein levels were matched by similar fluctuations in beta and beta(T) mRNAs. FcepsilonRIbeta is a key regulator of IgER expression and function, a gene in which polymorphisms correlate with allergic disease prevalence. The ability of IgE and FcepsilonRI signaling to coordinate expression of the beta and beta(T) subunits may comprise a homeostatic feedback loop-one that could promote chronic inflammation and allergic disease if dysregulated.
authors.affiliation: Department of Biology, Virginia Commonwealth University, Richmond, Virginia 23284-2012, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brenzovich
authors.forename: Matthew
authors.initials: M
authors.lastname: Macey
authors.forename: Josephine
authors.initials: J
authors.lastname: Fernando
authors.forename: Hey Jin
authors.initials: HJ
authors.lastname: Chong
authors.forename: Brian
authors.initials: B
authors.lastname: Barnstein
authors.forename: Paria
authors.initials: P
authors.lastname: Mirmonsef
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Morales
authors.forename: Akiko
authors.initials: A
authors.lastname: Kimura
authors.forename: Tracey Dawson
authors.initials: TD
authors.lastname: Cruz
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007152:Immunologic Capping / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000072377:Syk Kinase
chemical_list: D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D000072377:Syk Kinase; C000606897:Syk protein, mouse