Regulation of neutrophil apoptosis by cytokines: Role of IAP family

Abstract

Human neutrophils undergo spontaneous apoptosis, and spontaneous neutrophil apoptosis is delayed in the presence of various inflammatory cytokines, including G-CSF, GM-CSF, IFN-α and IFN-γ. These cytokines exert the antiapoptotic effect on human neutrophils in a protein-synthesis dependent mechanism, indicating that certain antiapoptotic molecules are up-regulated by stimulation with these cytokines. Human neutrophils express Bcl-2 family (Mcl-1, A1 and Bcl-X_L) and IAP (inhibitor of apoptosis) family (cIAP1, cIAP2, XIAP and survivin) members, both of which may be involved in cytokine-mediated anti-apoptotic effect. Among these molecules, cIAP2 is found to be selectively up-regulated by stimulation with G-CSF, IFN-α and IFN-γ via activation of the JAK2/STAT3 pathway, and overexpression of cIAP2 is detected in a patient with chronic neutrophilic leukemia.