title: Cutting edge: IL-4-mediated protection of primary B lymphocytes from apoptosis via Stat6-dependent regulation of glycolytic metabolism.
abstract: IL-4 prevents the death of naive B lymphocytes through the up-regulation of antiapoptotic proteins such as Bcl-x(L). Despite studies implicating glucose utilization in growth factor-dependent survival of hemopoietic cells, the role of glucose energy metabolism in maintaining B cell viability by IL-4 is unknown. We show that IL-4 triggers glucose uptake, Glut1 expression, and glycolysis in splenic B cells; this is accompanied by increased cellular ATP. Glycolysis inhibition results in apoptosis, even in the presence of IL-4. IL-4-induced glycolysis occurs normally in B cells deficient in insulin receptor substrate-2 or the p85alpha subunit of PI3K and is not affected by pretreatment with PI3K or MAPK pathway inhibitors. Stat6-deficient B cells exhibit impaired IL-4-induced glycolysis. Cell-permeable, constitutively active Stat6 is effective in restoring IL-4-induced glycolysis in Stat6-deficient B cells. Therefore, besides controlling antiapoptotic proteins, IL-4 mediates B cell survival by regulating glucose energy metabolism via a Stat6-dependent pathway.
authors.affiliation: Department of Biology, Boston college, Chestnut Hill, MA 02467, USA.
authors.forename: Fay J
authors.initials: FJ
authors.lastname: Dufort
authors.forename: Blair F
authors.initials: BF
authors.lastname: Bleiman
authors.forename: Maria R
authors.initials: MR
authors.lastname: Gumina
authors.forename: Derek
authors.initials: D
authors.lastname: Blair
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Wagner
authors.forename: Mary F
authors.initials: MF
authors.lastname: Roberts
authors.forename: Yousef
authors.initials: Y
authors.lastname: Abu-Amer
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chiles
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002470:Cell Survival / Q000276:immunology; D004734:Energy Metabolism / Q000276:immunology*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D005947:Glucose