A Paradoxical Effect of Interleukin-32 Isoforms on Cancer

Shim, Saerok; Lee, Siyoung; Hisham, Yasmin; Kim, Sinae; Nguyen, Tam T.; Taitt, Afeisha S.; Hwang, Jihyeong; Jhun, Hyunjhung; Park, Ho-Young; Lee, Young-Min; Yeom, Su Cheong; Kim, Sangjin; Kim, Soohyun

doi:10.3389/fimmu.2022.837590

Cited by 14 publications

(5 citation statements)

References 100 publications

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“…IL32 is a multifunctional cytokine with pleiotropic effects and higher circulating IL32 levels were observed in a variety of diseases in which it amplifies inflammatory response, such as rheumatoid arthritis, systemic sclerosis, inflammatory bowel disease and several cancers, but also in coronary artery disease [ 34 , 35 , 36 , 37 ]. In this respect, IL32 may play a role in endothelial cell function, and in the activation and proliferation associated wtith vasocontrisction and development of arterial hypertension.…”

Section: Discussionmentioning

confidence: 99%

Circulating Interlukin-32 and Altered Blood Pressure Control in Individuals with Metabolic Dysfunction

Tomasi

Cherubini

Pelusi

et al. 2023

IJMS

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Fatty liver disease is most frequently related to metabolic dysfunction (MAFLD) and associated comorbidities, heightening the risk of cardiovascular disease, and is associated with higher hepatic production of IL32, a cytokine linked with lipotoxicity and endothelial activation. The aim of this study was to examine the relationship between circulating IL32 concentration and blood pressure control in individuals with metabolic dysfunction at high risk of MAFLD. IL32 plasma levels were measured by ELISA in 948 individuals with metabolic dysfunction enrolled in the Liver-Bible-2021 cohort. Higher circulating IL32 levels were independently associated with systolic blood pressure (estimate +0.008 log10 per 1 mmHg increase, 95% c.i. 0.002–0.015; p = 0.016), and inversely correlated with antihypertensive medications (estimate −0.189, 95% c.i. −0.291–−0.088, p = 0.0002). Through multivariable analysis, IL32 levels predicted both systolic blood pressure (estimate 0.746, 95% c.i 0.173–1.318; p = 0.010) and impaired blood pressure control (OR 1.22, 95% c.i. 1.09–1.38; p = 0.0009) independently of demographic and metabolic confounders and of treatment. This study reveals that circulating IL32 levels are associated with impaired blood pressure control in individuals at risk of cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Circulating Interlukin-32 and Altered Blood Pressure Control in Individuals with Metabolic Dysfunction

Tomasi

Cherubini

Pelusi

et al. 2023

IJMS

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“…10). IL-32β is associated with hypoxic conditions in solid tumors and IL-32θ inhibits NF-kB which counters the epithelial-mesenchymal transition 30 .…”

Section: Surveying the Transcriptional Landscape Of An Ovarian Tumor ...mentioning

confidence: 99%

Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer

Byrne¹,

Le²,

Sereti³

et al. 2023

Preprint

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Single-cell RNA sequencing predominantly employs short-read sequencing to characterize cell types, states and dynamics; however, it is inadequate for comprehensive characterization of RNA isoforms. Long-read sequencing technologies enable single-cell RNA isoform detection but are hampered by lower throughput and unintended sequencing of artifacts. Here we developed Single-cell Targeted Isoform Long-Read Sequencing (scTaILoR-seq), a hybridization capture method which targets over a thousand genes of interest, improving the median number of unique transcripts per cell by 29-fold. We used scTaILoR-seq to identify and quantify RNA isoforms from ovarian cancer cell lines and primary tumors, yielding 10,796 single-cell transcriptomes. Using long-read variant calling we revealed associations of expressed single nucleotide variants (SNVs) with alternative transcript structures. In addition, phasing of SNVs across transcripts facilitated measurement of allelic imbalance within distinct cell populations. Overall, scTaILoR-seq is a long-read targeted RNA sequencing method and analytical framework for exploring transcriptional variation at single-cell resolution.

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“…Seven isoforms of IL-32 were described, among which IL-32-theta is the most active (Shim et al, 2022a). Since its discovery, IL-32 has been shown to be involved in host defense, inflammatory disease, and cancer (Joosten et al, 2013;Shim et al, 2022b). Soo Hyun Kim, our former PhD student who cloned the IL-18BP (now an independent scientist), offered me a collaboration to isolate the putative IL-32 receptor.…”

Section: Il-32 Binding Protein (2005)mentioning

confidence: 99%

Nine receptors and binding proteins, four drugs, and one woman: Historical and personal perspectives

Novick

2022

Front. Drug. Discov.

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In the era of bioinformatics and high-throughput techniques, it is tempting to forget the advantage of an old yet efficient and straightforward technique, ligand affinity chromatography, in the search for unknown proteins. This type of separation is based on an interaction between the target analyte potentially present in a crude mixture of proteins and a ligand coupled covalently to a resin. This process allows thousands-fold purification in a single step, which is crucial when using an extremely rich source of naturally occurring proteins such as human urine or plasma. Before the completion of The Genome Project, this method facilitated the rapid and reliable cloning of the corresponding gene based on the partial amino acid sequence of the isolated protein. Upon completion of this project, a partial protein sequence was enough to retrieve its complete mRNA and, hence, its complete protein sequence. Ligand affinity chromatography is indispensable for the isolation of both expected and unexpected binding proteins found by serendipity. My approach of combining a rich source of human proteins (1,000-fold concentrated human urine) together with this highly specific isolation method yielded proteins from both groups. The expected proteins included the two receptors for TNF (TBPI and TBPII), type I and type II interferon receptors (IFNα/βR, IFN-γR), and IL-6 and LDL receptors. The unexpected group of proteins included IL-18 binding protein (IL-18BP), IL-32 binding protein (Proteinase 3), and heparanase binding protein, the resistin. The discovery of the type I IFN receptor was a “eureka” moment in my life since it put an end to a 35-year worldwide search for this receptor. Using chemical purification methods, the TBPII might have never been discovered. Years later, TBPII was translated into the blockbuster drug Enbrel® to treat mainly rheumatoid arthritis. IFN-beta was translated into the blockbuster drug Rebif® to treat the autoimmune disease multiple sclerosis. IL-18BP translated into the drug Tadekinig alfa™ and is in a phase III clinical study for inflammatory and autoimmune pathologies. It has saved the lives of children born with mutations (NLRC4, XIAP) and is an example of personalized medicine. COVID-19 and CAR-T cytokine storms are the recent targets of IL-18BP.

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A Paradoxical Effect of Interleukin-32 Isoforms on Cancer

Cited by 14 publications

References 100 publications

Circulating Interlukin-32 and Altered Blood Pressure Control in Individuals with Metabolic Dysfunction

Circulating Interlukin-32 and Altered Blood Pressure Control in Individuals with Metabolic Dysfunction

Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer

Nine receptors and binding proteins, four drugs, and one woman: Historical and personal perspectives

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