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  • 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

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Basic Science
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
  1. Ting Lai, MD*,
  2. Kana Wang, MM*,
  3. Qiannan Hou, BMed*,
  4. Jian Zhang, MD*,
  5. Jialing Yuan, MM*,
  6. Lixing Yuan, BMed*,
  7. Zongbing You, MD, PhD† and
  8. Mingrong Xi, MD, PhD*
  1. * Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Sichuan, China; and
  2. † Departments of Structural & Cellular Biology and Orthopedic Surgery, Tulane Cancer Center, LCRC, Tulane Center for Aging, Tulane Center for Gene Therapy, Tulane University School of Medicine, New Orleans, LA.
  1. Address correspondence and reprint requests to Mingrong Xi, MD, PhD, Department of Obstetrics & Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China. E-mail: qmrjzz{at}126.com; or Zongbing You, MD, PhD, Departments of Structural & Cellular Biology and Orthopedic Surgery, Tulane Cancer Center, LCRC, Tulane Center for Aging, Tulane Center for Gene Therapy, School of Medicine, Tulane University, New Orleans, LA 70112. E-mail: zyou{at}tulane.edu.

Abstract

Objectives 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.

Methods 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.

Results 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.

Conclusion These results demonstrated that IL-17 may regulate chemokines and cytokines in gynecologic cancers.

  • IL-17
  • Gynecologic cancer
  • Chemokine
  • NF-κB
  • ERK1/2

http://dx.doi.org/10.1097/IGC.0b013e31822d2abd

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    Footnotes

    • The authors declare that no potential conflict of interest exists.