Role of interleukin‑32 in cancer biology (Review)

Yan, Haimeng; He, Donghua; Huang, Xi; Zhang, Enfan; Chen, Qingxiao; Xu, Rui‐hua; Liu, Xinling; Zi, Fuming; Zhang, Cai

doi:10.3892/ol.2018.8649

Cited by 21 publications

(20 citation statements)

References 67 publications

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“…The up-regulation of IL32 in current inhibitor subjects was also of particular interest, as only primates carry this gene. Furthermore, it has been implicated in inflammatory disorders such as rheumatoid arthritis, asthma (45), Graves' disease (46), viral infections (47,48), chronic psoriasis (49), and cancer (50). IL32 encodes interleukin (IL)-32, a cytokine containing an RGD sequence indicating a role in cell attachment via integrin binding, as well as in signaling.…”

Section: Discussionmentioning

confidence: 99%

Hemophilia A Inhibitor Subjects Show Unique PBMC Gene Expression Profiles That Include Up-Regulated Innate Immune Modulators

et al. 2020

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Formation of pathological anti-FVIII antibodies, or "inhibitors," is the most serious complication of therapeutic FVIII infusions, affecting up to 1/3 of severe Hemophilia A (HA) patients. Inhibitor formation is a classical T-cell dependent adaptive immune response. As such, it requires help from the innate immune system. However, the roles of innate immune cells and mechanisms of inhibitor development vs. immune tolerance, achieved with or without Immune Tolerance Induction (ITI) therapy, are not well-understood. To address these questions, temporal transcriptomics profiling of FVIII-stimulated peripheral blood mononuclear cells (PBMCs) was carried out for HA subjects with and without a current or historic inhibitor using RNA-Seq. PBMCs were isolated from 40 subjects in the following groups: HA with an inhibitor that resolved either following ITI or spontaneously; HA with a current inhibitor; HA with no inhibitor history and non-HA controls. PBMCs were stimulated with 5 nM FVIII and RNA was isolated 4, 16, 24, and 48 h following stimulation. Time-series differential expression analysis was performed and distinct transcriptional signatures were identified for each group, providing clues as to cellular mechanisms leading to or accompanying their disparate anti-FVIII antibody responses. Subjects with a current inhibitor showed differential expression of 56 genes and a clustering analysis identified three major temporal profiles. Interestingly, gene ontology enrichments featured innate immune modulators, including NLRP3, TLR8, IL32, CLEC10A, and COLEC12. NLRP3 and TLR8 are associated with enhanced secretion of the pro-inflammatory cytokines IL-1β and TNFα, while IL32, which has several isoforms, has been associated with both inflammatory and regulatory immune processes. RNA-Seq results were validated by RT-qPCR, ELISAs, multiplex cytokine analysis, and flow cytometry. The inflammatory status of HA patients suffering from an ongoing inhibitor includes up-regulated innate immune modulators, which may act as ongoing danger signals that influence the responses to, and eventual outcomes of, ITI therapy.

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Section: Discussionmentioning

confidence: 99%

Hemophilia A Inhibitor Subjects Show Unique PBMC Gene Expression Profiles That Include Up-Regulated Innate Immune Modulators

et al. 2020

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“…The high-risk variant of HPV induces IL-32 expression via E7-mediated cyclooxygenase 2 stimulation [97] . IL-32 may indirectly promote tumor angiogenesis via inducing other cytokines and growth factors that it is crucial in the pathogenesis and progression of cancer [98] .…”

Section: In-situ Cervical Cytokines In Cin and Cervical Cancermentioning

confidence: 99%

In situ immunopathological events in human cervical intraepithelial neoplasia and cervical cancer: Review

Carrero

Callejas

Mosquera

2021

Translational Oncology

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Highlights Neoplasia of the cervix is one of the most frequent in women. Immunological impairment in cervical intraepithelial neoplasia and cancer have been reported. In-situ expression of cytokines and leukocytes during the cervical neoplasia occurs. Some of these cytokines can prevent or induce the progression of the neoplasm. Possible role in therapeutics of cervical cancer by cytokine manipulations need to be evaluated.

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“…One such gene is IL32, which encodes a cytokine that induces other proinflammatory cytokines to activate the NF-κB pathway (Ca and Sh, 2006;Yan et al, 2018). IL32 is more highly expressed with increasing African ancestry in all cell types following infection (lsfr < 8.8x10 -6 ) (Fig.…”

Section: Genetic Ancestry Is Associated With the Transcriptional Immumentioning

confidence: 99%

Single-cell RNA-sequencing reveals pervasive but highly cell type-specific genetic ancestry effects on the response to viral infection

Randolph

Fiege

et al. 2020

Preprint

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Humans vary in their susceptibility to infectious disease, partly due to variation in the immune response following infection. Here, we used single-cell RNA-sequencing to quantify genetic contributions to this variation in peripheral blood mononuclear cells, focusing specifically on the transcriptional response to influenza infection. We find that monocytes are the most responsive to influenza infection, but that all cell types mount a conserved interferon response, which is stronger in individuals with increased European ancestry. By comparing European American and African American individuals, we show that genetic ancestry effects on expression are common, influencing 29% of genes, but highly cell type-specific. Further, we demonstrate that much of this population-associated expression variation is explained by cis expression quantitative trait loci, which are enriched for signatures of recent positive selection. Our findings establish common cis-regulatory variants—including those that are differentiated by genetic ancestry—as important determinants of the antiviral immune response.

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Role of interleukin‑32 in cancer biology (Review)

Cited by 21 publications

References 67 publications

Hemophilia A Inhibitor Subjects Show Unique PBMC Gene Expression Profiles That Include Up-Regulated Innate Immune Modulators

Hemophilia A Inhibitor Subjects Show Unique PBMC Gene Expression Profiles That Include Up-Regulated Innate Immune Modulators

In situ immunopathological events in human cervical intraepithelial neoplasia and cervical cancer: Review

Single-cell RNA-sequencing reveals pervasive but highly cell type-specific genetic ancestry effects on the response to viral infection

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