Regulation of interleukin-8 expression in melanoma-stimulated neutrophil inflammatory response

Inflammation facilitates tumor progression including metastasis. Interleukin-8 (IL-8) is a chemokine that regulates polymorphonuclear neutrophil (PMN) mobilization and activity and we hypothesize that this cytokine influences tumor behavior. We have demonstrated that IL-8 is crucial for PMN-mediated melanoma extravasation under flow conditions. In addition, IL-8 is up-regulated in PMNs upon co-culturing with melanoma cells. Melanoma cells induce IκB-α degradation in PMNs indicating that NF-κB signaling is active in PMNs. Furthermore, the production of IL-8 in PMNs is NF-κB dependent. We have further identified that interleukin-6 (IL-6) and interleukin-1β (IL-1β) from PMN-melanoma co-cultures synergistically contribute to IκB-α degradation and IL-8 synthesis in PMNs. Taken together, these findings show that melanoma cells induce PMNs to secrete IL-8 through activation of NF-κB and suggest a model in which this interaction promotes a microenvironment that is favorable for metastasis.