Molecular interactions and functions of IL-32

Aass, Kristin Roseth; Kastnes, Martin H.; Standal, Therese

doi:10.1002/jlb.3mr0620-550r

Cited by 48 publications

(53 citation statements)

References 162 publications

(587 reference statements)

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“…IL-32 has different isoforms 13 and based on RNA-sequencing several isoforms are expressed in the three cell lines. INA-6 cells express IL-32β and IL-32γ, with the highest expression of the β-isoform (Supplementary Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

“…An IL-32 receptor is not identified, and it is not entirely clear how IL-32 acts at the molecular level 13 . Thus, to identify IL-32 binding partners we performed co-immunoprecipitation of endogenously expressed IL-32 followed by mass spectrometry analyses of the precipitates.…”

Section: Resultsmentioning

confidence: 99%

“…IL-32 has no sequence homology with other cytokine families, and an IL-32 receptor has not been identified. The secreted form of IL-32 acts like a cytokine, but IL-32 also have distinct intracellular functions 13 . For example, IL-32 was detected in the mitochondrial fraction of breast cancer cells and improved the metabolic fitness of the cells during hypoxic stress 14 .…”

Section: Introductionmentioning

confidence: 99%

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IL-32 is a metabolic regulator promoting survival and proliferation of malignant plasma cells

Aass

Mjelle

Kastnes

et al. 2021

Preprint

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IL-32 is a non-classical cytokine expressed in cancers, inflammatory diseases and infections. IL-32 can have both extracellular and intracellular functions, and its receptor is not identified. We here demonstrate that endogenously expressed, intracellular IL-32 binds to components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in malignant plasma cells significantly reduced survival and proliferation in vitro and in vivo. High throughput transcriptomic and MS-metabolomic profiling of IL-32 KO cells revealed that loss of IL-32 leads to profound perturbations in metabolic pathways, with accumulation of lipids, pyruvate precursors and citrate, indicative of reduced mitochondrial function. IL-32 is expressed in a subgroup of multiple myeloma patients with an inferior prognosis. Primary myeloma cells expressing IL-32 were characterized by a plasma cell gene signature associated with immune activation, proliferation and oxidative phosphorylation. We propose a novel concept for regulation of metabolism by an intracellular cytokine and identify IL-32 as an endogenous growth and survival factor for malignant plasma cells. IL-32 is a potential prognostic biomarker and a treatment target in multiple myeloma.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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IL-32 is a metabolic regulator promoting survival and proliferation of malignant plasma cells

Aass

Mjelle

Kastnes

et al. 2021

Preprint

Self Cite

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“…When we compared HS patients with and without inflammatory complications, there were some apparent differences at the transcriptomic level between HS1 and HS2, demonstrated by several DEGs, such as ADAM19, CCL17, CCL19, CXCL5, IL32, MEG3, MMP12, and NINL. Collectively these genes can control the cell migration in response to inflammatory stimuli [24,25] and induce an inflammatory response [26][27][28]. All of these actions may account for the development of the autoinflammatory phenotype and RDD.…”

Section: Discussionmentioning

confidence: 99%

Identification of Critical Transcriptomic Signaling Pathways in Patients with H Syndrome and Rosai-Dorfman Disease

et al. 2020

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Biallelic mutations in SLC29A3 cause histiocytosis-lymphadenopathy plus syndrome, also known as H syndrome (HS). HS is a complex disorder, with ~ 25% of patients developing autoinflammatory complications consisting of unexplained fevers, persistently elevated inflammatory markers, and unusual lymphadenopathies, with infiltrating CD68+, S100+, and CD1a− histiocytes, resembling the immunophenotype found in Rosai-Dorfman disease (RDD). We investigated the transcriptomic profiles of monocytes, non-activated (M0), classically activated (M1), and alternatively activated macrophages (M2) in two patients with HS, one without autoinflammatory (HS1) and one with autoinflammatory complications (HS2). RNA sequencing revealed a dysregulated transcriptomic profile in both HS patients compared to healthy controls (HC). HS2, when compared to HS1, had several differentially expressed genes, including genes associated with lymphocytic-histiocytic predominance (e.g. NINL) and chronic immune activation (e.g. B2M). The transcriptomic and cytokine profiles of HS patients were comparable to patients with SAID with high levels of TNF. SERPINA1 gene expression was found to be upregulated in all patients studied. Moreover, higher levels of IFNγ were found in the serum of both HS patients when compared to HC. Gene ontology (GO) enrichment analysis of the DEGs in HS patients revealed the terms “type I IFN,” “IFNγ signaling pathway,” and “immune responses” as the top 3 most significant terms for monocytes. Gene expression analysis of lymph node biopsies from sporadic and H syndrome-associated RDD suggests common underlying pathological process. In conclusion, monocytes and macrophages from both HS patients showed transcriptomic profiles similar to SAIDs and also uniquely upregulated IFNγ signature. These findings may help find better therapeutic options for this rare disorder.

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“…Interleukin-32 was identified primarily as NK cell transcript 4 (NK4) expressed in T lymphocytes and NK cells [ 83 ]. It exists in nine splice variants, formed as a result of the alternative splicing of eight exons [ 211 ].…”

Section: Interleukinsmentioning

confidence: 99%

Melanoma Progression under Obesity: Focus on Adipokines

Olszańska

Pietraszek-Gremplewicz

Nowak

2021

Cancers

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Obesity is a growing problem in the world and is one of the risk factors of various cancers. Among these cancers is melanoma, which accounts for the majority of skin tumor deaths. Current studies are looking for a correlation between obesity and melanoma. They suspect that a potential cause of its development is connected to the biology of adipokines, active molecules secreted by adipose tissue. Under physiological conditions, adipokines control many processes, including lipid and glucose homeostasis, insulin sensitivity, angiogenesis, and inflammations. However, when there is an increased amount of fat in the body, their secretion is dysregulated. This article reviews the current knowledge of the effect of adipokines on melanoma growth. This work focuses on the molecular pathways by which adipose tissue secreted molecules modify the angiogenesis, migration, invasion, proliferation, and death of melanoma cells. We also discuss the role of these factors as markers of incidence, metastasis, and melanoma patient survival. Understanding the functions of adipokines will lead to knowledge of whether and how obesity promotes melanoma growth. Further studies may contribute to the innovations of therapies and the use of adipokines as predictive and/or prognostic biomarkers.

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Molecular interactions and functions of IL-32

Cited by 48 publications

References 162 publications

IL-32 is a metabolic regulator promoting survival and proliferation of malignant plasma cells

IL-32 is a metabolic regulator promoting survival and proliferation of malignant plasma cells

Identification of Critical Transcriptomic Signaling Pathways in Patients with H Syndrome and Rosai-Dorfman Disease

Melanoma Progression under Obesity: Focus on Adipokines

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