IL-32 is induced by activation of toll-like receptors in multiple myeloma cells

Kristin Roseth Aass; Synne Stokke Tryggestad; Robin Mjelle; Martin H Kastnes; Tonje Marie Vikene Nedal; Kristine Misund; Therese Standal

doi:10.3389/fimmu.2023.1107844

IL-32 is induced by activation of toll-like receptors in multiple myeloma cells

Front Immunol. 2023 Feb 16:14:1107844. doi: 10.3389/fimmu.2023.1107844. eCollection 2023.

Authors

Kristin Roseth Aass¹, Synne Stokke Tryggestad¹, Robin Mjelle^{1

2

3}, Martin H Kastnes¹, Tonje Marie Vikene Nedal¹, Kristine Misund¹, Therese Standal^{1

4}

Affiliations

¹ Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
² Bioinformatics Core Facility - BioCore, Norwegian University of Science and Technology, Trondheim, Norway.
³ Department of Pathology, St. Olavs University Hospital, Trondheim, Norway.
⁴ Department of Hematology, St. Olavs University Hospital, Trondheim, Norway.

Abstract

Multiple myeloma (MM) is a hematological cancer characterized by accumulation of malignant plasma cells in the bone marrow. The patients are immune suppressed and suffer from recurrent and chronic infections. Interleukin-32 is a non-conventional, pro-inflammatory cytokine expressed in a subgroup of MM patients with a poor prognosis. IL-32 has also been shown to promote proliferation and survival of the cancer cells. Here we show that activation of toll-like receptors (TLRs) promotes expression of IL-32 in MM cells through NFκB activation. In patient-derived primary MM cells, IL-32 expression is positively associated with expression of TLRs. Furthermore, we found that several TLR genes are upregulated from diagnosis to relapse in individual patients, predominantly TLRs sensing bacterial components. Interestingly, upregulation of these TLRs coincides with an increase in IL-32. Taken together, these results support a role for IL-32 in microbial sensing in MM cells and suggest that infections can induce expression of this pro-tumorigenic cytokine in MM patients.

Keywords: IL-32; NFκB; TLR; cancer; cytokine; inflammation; multiple myeloma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines
Humans
Interleukins
Multiple Myeloma*
Signal Transduction
Toll-Like Receptors

Substances

Interleukins
Toll-Like Receptors
Cytokines

Grants and funding

This work was supported by funds from the Norwegian Cancer Society (#198161), The Research Council of Norway (# 274991, #223255), The Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology (# 90171600, #90635300 #30171600), and the Cancer Fund at St.Olavs Hospital.