title: IL-4 and IL-10 inhibition of spontaneous monocyte apoptosis is associated with Flip upregulation.
abstract: Human peripheral blood monocytes undergo spontaneous apoptosis in culture. Spontaneous monocyte apoptosis is regulated by the death ligand, Fas Ligand (FasL) binding to its receptor Fas. The pro-inflammatory molecules, LPS and IL-1beta, prevent spontaneous monocyte apoptosis. Here, we demonstrate that the anti-inflammatory cytokines IL-4 and IL-10 inhibit spontaneous monocyte apoptosis compared to control-treated cells. IL-4- or IL-10-mediated suppression of spontaneous monocyte apoptosis is associated with the induction of Flip, an essential inhibitor of the Fas-death signal. In contrast, IL-4 and IL-10 inhibit LPS or IL-1beta induced pro-inflammatory cytokine production. These data suggest that in monocytes IL-4 or IL-10 has a dual function, to inhibit pro-inflammatory cytokine production and to suppress spontaneous apoptosis.
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, Saint Louis University, 1402 South Grand Blvd, Saint Louis, Missouri 63104, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Eslick
authors.forename: John C
authors.initials: JC
authors.lastname: Scatizzi
authors.forename: Lee
authors.initials: L
authors.lastname: Albee
authors.forename: Emily
authors.initials: E
authors.lastname: Bickel
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bradley
authors.forename: Harris
authors.initials: H
authors.lastname: Perlman
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016753:Interleukin-10; D015847:Interleukin-4