Regulation of interleukin-8 expression in melanoma-stimulated neutrophil inflammatory response |
| |
Authors: | Peng Hsin-Hsin Liang Shile Henderson Andrew J Dong Cheng |
| |
Institution: | Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802, USA. |
| |
Abstract: | 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 IkappaB-alpha degradation in PMNs indicating that NF-kappaB signaling is active in PMNs. Furthermore, the production of IL-8 in PMNs is NF-kappaB dependent. We have further identified that interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) from PMN-melanoma co-cultures synergistically contribute to IkappaB-alpha 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-kappaB and suggest a model in which this interaction promotes a microenvironment that is favorable for metastasis. |
| |
Keywords: | Cancer Chemokines Extravasation Immunoediting Interleukin-1β (IL-1β) Interleukin-6 (IL-6) Nuclear factor-κB (NF-κB) Signaling |
本文献已被 ScienceDirect PubMed 等数据库收录! |