title: Flice inhibitory protein is associated with the survival of neonatal neutrophils.
abstract: Neonatal polymorphonuclear leukocytes (PMN) exhibit delayed apoptosis both constitutively and under inflammatory conditions, and evidence has linked PMN longevity to the presence of antiapoptotic proteins. Activation of the survival-associated transcription factor, nuclear factor kappa B (NF-κB), promotes the synthesis of several antiapoptotic proteins including Flice inhibitory protein (FLIP). Neonatal and adult PMN were compared in this study to test the hypothesis that FLIP modulates age-related apoptosis. Expression of the short isoform, FLIP-S, was prominent at baseline and persisted during spontaneous apoptosis in neonatal PMN, whereas basal expression was lower and decreased under the same conditions in adult PMN. Stable FLIP-S expression in neonatal PMN was associated with a relative resistance to apoptosis in response to the protein synthesis inhibitor, cycloheximide (CHX), or the NF-κB inhibitor, gliotoxin. In contrast, similar treatment of adult PMN promoted greater overall apoptosis accompanied by FLIP degradation. Nuclear levels of phosphorylated p65, a critical NF-κB dimer, were relatively robust in neonatal PMN under basal conditions or after stimulation with TNF-α, a cytokine that induces FLIP. In conclusion, persistent FLIP-S expression is involved in the longevity of neonatal PMN, and our data suggest a contribution of NF-κB signaling and related survival mechanisms.
authors.affiliation: Department of Pediatrics, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Rashmi
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Schnulle
authors.forename: Allison C
authors.initials: AC
authors.lastname: Maddox
authors.forename: Eric S
authors.initials: ES
authors.lastname: Armbrecht
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Koenig
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D020033:Protein Isoforms / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D016328:NF-kappa B; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide