X-rays induced IL-8 production in lung cancer cells via p38/MAPK and NF-κB pathway

Int J Radiat Biol. 2020 Nov;96(11):1374-1381. doi: 10.1080/09553002.2020.1683643. Epub 2020 Jan 6.

Abstract

Purpose: It is reported inflammatory cytokine interleukin-8 (IL-8) could predict radiation-induced lung toxicity (RILT). RILT is believed to be a consequence of a cascade of cytokine production. It is considered that vascular endothelial cell and macrophages are the mainly source of cytokines. This study was investigated the production of IL-8 from cancer cells induced by X-rays may involve in the radiation-induced inflammation.

Materials and methods: We analyzed IL-8 in human lung cancer cell lines after expose to X-rays, and we also detect IL-8 in HUVEC cells and THP1 cells as endothelial cell and macrophage model to identify the change in normal cells after expose. Furthermore, we added the inhibitors to the culture with or without radiation to identify the role of MAPK and NF-κB pathways on the radiation-induced secretion of IL-8.

Results: Radiation could induce IL-8 production both in non-lung cancer cells (HUVECs and THP1 cells) and in lung cancer cells (A549 cells, H446 cells, PC-9 cells). Simultaneously, radiation activated p38/MAPK and NF-κB signal pathways in lung cancer cells. Moreover, p38/MAPK inhibitor SB203580 and NF-κB inhibitor BAY11-7082 could block the IL-8 up-regulated by X-rays but JNK inhibitor SP600125, ERK inhibitor U0126, ROS Scavenger NAC could not inhibit this phenomenon.

Conclusions: X-rays could induce IL-8 production in lung cancer cells, which may be related to the activation of p38/MAPK and NF-κB signaling pathway, providing a new point for elucidating the mechanism of radiation pneumonitis.

Keywords: IL-8; NF-κB; X-rays; p38/MAPK; radiation induced lung injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Interleukin-8 / biosynthesis*
  • Lung Neoplasms / pathology*
  • MAP Kinase Signaling System / radiation effects*
  • NF-kappa B / metabolism*
  • X-Ray Therapy*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Interleukin-8
  • NF-kappa B
  • p38 Mitogen-Activated Protein Kinases