Macrophage/microglia-derived IL-1β induces glioblastoma growth via the STAT3/NF-κB pathway

Hum Cell. 2022 Jan;35(1):226-237. doi: 10.1007/s13577-021-00619-8. Epub 2021 Sep 30.

Abstract

Glioblastoma is a glioma characterized by highly malignant features. Numerous studies conducted on the relationship between glioblastoma and the microenvironment have indicated the significance of tumor-associated macrophages/microglia (TAMs) in glioblastoma progression. Since interleukin (IL)-1β secreted by TAMs has been suggested to promote glioblastoma growth, we attempted to elucidate the detailed mechanisms of IL-1β in glioblastoma growth in this study. A phospho-receptor tyrosine kinase array and RNA-sequencing studies indicated that IL-1β induced the activation of signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. Glioblastoma cells stimulated by IL-1β induced the production of IL-6 and CXCL8, which synergistically promoted glioblastoma growth via signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. By immunohistochemistry, IL-1β expression was seen on TAMs, especially in perinecrotic areas. These results suggest that IL-1β might be a useful target molecule for anti-glioblastoma therapy.

Keywords: CXCL8; Glioblastoma; IL-1β; IL-6; Macrophage.

MeSH terms

  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Cell Line
  • Gene Expression
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Glioblastoma / therapy
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / physiology*
  • Macrophages / metabolism*
  • Microglia / metabolism*
  • Molecular Targeted Therapy
  • NF-kappa B / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / genetics*
  • Signal Transduction / physiology*

Substances

  • Interleukin-1beta
  • NF-kappa B
  • STAT3 Transcription Factor
  • STAT3 protein, human