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

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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.

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Acknowledgements

We thank Dr. Daisuke Kurotaki (IRCMS, Kumamoto University), Mr. Takenobu Nakagawa and Ms. Michiyo Tokunaga for technical assistance. This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (nos. 20H03459[Y.K] and 20H03792[A.M]).

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Authors and Affiliations

  1. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto Chuo-ku, Kumamoto, 860-8556, Japan

    Keitaro Kai, Yoshihiro Komohara & Yukio Fujiwara

  2. Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Keitaro Kai, Takahiro Yamamoto, Ken Uekawa, Kazutaka Ohta, Tatsuya Takezaki, Junichiro Kuroda, Naoki Shinojima, Tadashi Hamasaki & Akitake Mukasa

  3. Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, Japan

    Yoshihiro Komohara

  4. Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Shigeyuki Esumi

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  1. Keitaro Kai
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  2. Yoshihiro Komohara
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  3. Shigeyuki Esumi
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Correspondence to Yoshihiro Komohara.

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None of the authors have any conflicts of interest in association with this manuscript.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All patients provided informed consent in accordance with protocols of the Kumamoto University Review Board, and the study design was approved by the Kumamoto University Review Board (approval no. 1174).

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Kai, K., Komohara, Y., Esumi, S. et al. Macrophage/microglia-derived IL-1β induces glioblastoma growth via the STAT3/NF-κB pathway. Human Cell 35, 226–237 (2022). https://doi.org/10.1007/s13577-021-00619-8

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  • DOI: https://doi.org/10.1007/s13577-021-00619-8

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