Interleukin 17 Induces Up-Regulation of Chemokine and Cytokine Expression Via Activation of the Nuclear Factor κB and Extracellular Signal–Regulated Kinase 1/2 Pathways in Gynecologic Cancer Cell Lines

Abstract

Previous studies have revealed that interleukin 17 (IL-17) contributes to pathological processes in many solid tumors. However, the roles of IL-17 in gynecologic cancer still remain elusive, hindering the deep understanding of gynecologic tumorigenesis. In the present study, to delineate the functional roles of IL-17 in gynecologic cancer, IL-17 stimulation was introduced in cell lines of 3 gynecologic cancers, and IL-17-induced expression of chemokines and cytokines and possible signaling pathways were investigated. Our results showed that in HEC-1-B (human endometrial cancer) cells, IL-17 stimulation induced mRNA level increases of CCL2, CCL5, CCL20, CXCL2, and IL-8. Similar treatment in HeLa cells caused increases in the mRNA levels of CCL2, CXCL2, IL-6, and IL-8, and in SKOV3 cells, mRNA levels of CCL2, CCL20, CXCL1, CXCL2, IL-6, and IL-8 increased. The increases in mRNA levels induced by IL-17 were dose- and time-dependent. Furthermore, with the addition of the NF-κB (nuclear factor κ-light-chain-enhancer of activated B) and extracellular signal-regulated kinase inhibitors pyrrolidine dithiocarbamate and PD98059, the IL-17-induced CCL2 mRNA level was significantly compromised. IL-17 stimulation also activated phosphorylation of IκBα and extracellular signal-regulated kinase 1/2 in a time-dependent manner. These results demonstrated that IL-17 may regulate chemokines and cytokines in gynecologic cancers.