Abstract
Interleukin-1 (IL-1) plays a central role in the immune and inflammatory responses, and activates various types of cells, including human neutrophils. IL-1β exerts its effects through IL-1 receptor type I, and activates NF-κB and mitogen-activated protein kinase (MAPK) cascades. In human neutrophils, it was found that the MKK3/6-p38 MAPK cascade was selectively activated by IL-1β, and p38 MAPK activation mediated IL-1β-induced superoxide (O2-) release and up-regulation of CD11b (β2 integrin) and CD15 (a ligand for P-selectin). Our recent studies also show that stimulation of human neutrophils with various cytokines, including granulocyte colonystimulating factor, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-α, results in cytokine-specific activation of distinct MAPK subtype cascades, and that extracellular signal-regulated kinase as well as p38 MAPK mediates cytokine-induced O2- release and adherence. In this review, we discuss the signaling pathways activated by IL-1β and the role of MAPK subtype cascades and JAK-STAT pathway in activation of human neutrophils by inflammatory cytokines.
