IL-32 is induced by activation of toll-like receptors in multiple myeloma cells
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...
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Frontiers Media S.A.
2023-02-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107844/full |
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author | Kristin Roseth Aass Synne Stokke Tryggestad Robin Mjelle Robin Mjelle Robin Mjelle Martin H. Kastnes Tonje Marie Vikene Nedal Kristine Misund Therese Standal Therese Standal |
author_facet | Kristin Roseth Aass Synne Stokke Tryggestad Robin Mjelle Robin Mjelle Robin Mjelle Martin H. Kastnes Tonje Marie Vikene Nedal Kristine Misund Therese Standal Therese Standal |
author_sort | Kristin Roseth Aass |
collection | DOAJ |
description | 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. |
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format | Article |
id | doaj.art-ad856e22ff75450697d0815a497d6020 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-10T10:01:28Z |
publishDate | 2023-02-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
spelling | doaj.art-ad856e22ff75450697d0815a497d60202023-02-16T08:10:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11078441107844IL-32 is induced by activation of toll-like receptors in multiple myeloma cellsKristin Roseth Aass0Synne Stokke Tryggestad1Robin Mjelle2Robin Mjelle3Robin Mjelle4Martin H. Kastnes5Tonje Marie Vikene Nedal6Kristine Misund7Therese Standal8Therese Standal9Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayBioinformatics Core Facility - BioCore, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Pathology, St. Olavs University Hospital, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Hematology, St. Olavs University Hospital, Trondheim, NorwayMultiple 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107844/fullmultiple myelomaTLRinflammationIL-32NFκBcancer |
spellingShingle | Kristin Roseth Aass Synne Stokke Tryggestad Robin Mjelle Robin Mjelle Robin Mjelle Martin H. Kastnes Tonje Marie Vikene Nedal Kristine Misund Therese Standal Therese Standal IL-32 is induced by activation of toll-like receptors in multiple myeloma cells Frontiers in Immunology multiple myeloma TLR inflammation IL-32 NFκB cancer |
title | IL-32 is induced by activation of toll-like receptors in multiple myeloma cells |
title_full | IL-32 is induced by activation of toll-like receptors in multiple myeloma cells |
title_fullStr | IL-32 is induced by activation of toll-like receptors in multiple myeloma cells |
title_full_unstemmed | IL-32 is induced by activation of toll-like receptors in multiple myeloma cells |
title_short | IL-32 is induced by activation of toll-like receptors in multiple myeloma cells |
title_sort | il 32 is induced by activation of toll like receptors in multiple myeloma cells |
topic | multiple myeloma TLR inflammation IL-32 NFκB cancer |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107844/full |
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