Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells.

Leukotactin-1 (Lkn-1)/CCL15 is a recently cloned CC-chemokine that binds to the CCR1 and CCR3. Although Lkn-1 has been known to function as a chemoattractant for neutrophils, monocytes and lymphocytes, its cellular mechanism remains unclear. To understand the mechanism of Lkn-1-induced chemotaxis signaling, we examined the chemotactic activities of human osteogenic sarcoma cells expressing CCR1 in response to Lkn-1 using inhibitors of signaling molecules. Inhibitors of G(i)/G(o) protein, phospholipase C (PLC) and protein kinase Cdelta (PKCdelta) inhibited the chemotactic activity of Lkn-1 indicating that Lkn-1-induced chemotaxis signal is transduced through G(i)/G(o) protein, PLC and PKCdelta. The activities of PLC and PKCdelta were also enhanced by Lkn-1 stimulation. Chemotactic activity of Lkn-1 was inhibited by the treatment of cycloheximide and actinomycin D suggesting that newly synthesized proteins are needed for chemotaxis. Nuclear factor-kappaB (NF-kappaB) inhibitor reduced chemotactic activity of Lkn-1. DNA binding activity of NF-kappaB was also enhanced by Lkn-1 stimulation. These results suggest that Lkn-1 transduces the signal through G(i)/G(o) protein, PLC, PKCdelta, NF-kappaB and newly synthesized proteins for chemotaxis.