Interleukin-15 inhibits spontaneous apoptosis in human eosinophils via autocrine production of granulocyte macrophage-colony stimulating factor and nuclear factor-kappaB activation.
Prolonged eosinophil survival, i.e., reduced apoptosis, is implicated in the pathogenesis of chronic allergic inflammation. Here we demonstrate that interleukin (IL)-15, in the presence or absence of tumor necrosis factor (TNF)-alpha, reduces spontaneous apoptosis in freshly isolated human eosinophils. The prosurvival effect of IL-15 was abrogated by neutralizing antibody to granulocyte macrophage-colony stimulating factor (GM-CSF), although GM-CSF was not detected in conditioned media by ELISA. Additionally, the effect of IL-15 on spontaneous eosinophil apoptosis appeared to require nuclear factor-kappaB (NF-kappaB) activation based on evidence for NF-kappaB nuclear translocation and abrogation of the effect by the NF-kappaB inhibitor, Bay 11- 7082. Finally, the data demonstrate that IL-15 expression is higher in the submucosa of endobronchial tissues from subjects with moderate to severe asthma when compared with control subjects. Thus, our results suggest that IL-15, either alone or in combination with TNF-alpha, may perpetuate allergic inflammation by reduction of spontaneous eosinophil apoptosis through autocrine production of GM-CSF and NF-kappaB activation.
Hoontrakoon
Raweewan
R
Department of Pediatrics, Division of Allergy and Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Chu
Hong Wei
HW
Gardai
Shyra J
SJ
Wenzel
Sally E
SE
McDonald
Patrick
P
Fadok
Valerie A
VA
Henson
Peter M
PM
Bratton
Donna L
DL
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism* / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D019409:Interleukin-15; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor