INTERLEUKIN-8 STIMULATES CALCIUM TRANSIENTS AND PROMOTES EPIDERMAL-CELL PROLIFERATION

The presence of large amounts of biologically active interleukin-8 (IL-8) in psoriatic involved skin suggests that it may contribute, in part, to the changes observed in psoriasis, including hyperproliferation of keratinocytes. To examine the effect of IL-8 on epidermal growth, we monitored cytosolic free Ca++ transients in human keratinocytes adult skin epidermis calcium reduced level, temperature elevated (HaCat) cells and normal keratinocytes loaded with the cell permeable, acetoxymethyl derivative, indo-1AM. Addition of IL-8 (0.06 - 47 nM) to the HaCat cells induced rapid rises in cytosolic free Ca++ from resting levels of 145 +/- 38 to peak levels of 889 +/- 10 nM. The induced rises in Ca++ were transient and concentration dependent. Half maximal effect was observed at 1.2 nM. Normal keratinocytes also responded to IL-8 (6 nM) by rises in cytosolic free Ca++ from a pre-stimulated level of 269 nM to transient peak value of 393 nM. In addition, IL-8 promoted epidermal cell proliferation. Polyclonal anti-IL-8 antibody blocked IL-8-induced calcium changes and proliferation. Under similar conditions, human neutrophils also responded to IL-8 in a similar dose range by a rapid and transient mobilization of Ca++. The findings indicate that IL-8 has a wider range of responsive target cells than hitherto thought and acts as an autocrine growth factor.