Type I and type II interferons delay human neutrophil apoptosis via activation of STAT3 and up-regulation of cellular inhibitor of apoptosis 2

We have recently demonstrated that granulocyte‐colony stimulating factor (G‐CSF) delays human neutrophil apoptosis via up‐regulation of cellular inhibitor of apoptosis 2 (cIAP2), which is dependent on activation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Here, we show that type I and type II interferons (IFNs), which bind to the distinct receptors, exert the antiapoptotic effect on human neutrophils through the similar mechanism. IFN‐α (type I IFN) and IFN‐γ (type II IFN), like G‐CSF, delayed human neutrophil apoptosis through the protein synthesis‐dependent mechanism. Stimulation of neutrophils with IFN‐α or IFN‐γ resulted in tyrosine phosphorylation of STAT1 and STAT3 but not phosphorylation of STAT5, Akt, extracellular signal‐regulated kinase, and p38 mitogen‐activated protein kinase. IFN‐α and IFN‐γ induced the expression of transcripts of cIAP2 and suppressor of cytokine signaling 1 and 3, but not cIAP1, Mcl‐1, and A1. IFN‐α‐ and IFN‐γ‐induced up‐regulation of cIAP2 mRNA and protein, phosphorylation of STAT3, and antiapoptotic effect were inhibited significantly by pretreatment of cells with AG490, a specific inhibitor of JAK2. These findings suggest that cIAP2 expression is up‐regulated by IFN‐α and IFN‐γ through, at least in part, activation of the JAK2‐STAT3 pathway, and increased expression of the cIAP2 protein may contribute to an IFN‐α‐ and IFN‐γ‐mediated antiapoptotic effect on human neutrophils.