IL-32, a novel cytokine with a possible role in disease

Dinarello, Charles A.; Kim, S.-H.

doi:10.1136/ard.2006.058511

Cited by 154 publications

(175 citation statements)

References 29 publications

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“…Consistent with this, we observed reductions in the mRNA of IL32, a hormone secreted by natural killer and T lymphocytes (Dinarello & Kim 2006). We also observed a downregulation in transcripts that are interferon-gamma dependent.…”

Section: Inflammationsupporting

confidence: 74%

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Hochberg

Harvey

Tran

et al. 2016

EJEA

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Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the subcutaneous adipose tissue from patients with Cushing's disease (nZ5) compared to patients with nonfunctioning pituitary adenomas (nZ11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.

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Section: Inflammationsupporting

confidence: 74%

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Hochberg

Harvey

Tran

et al. 2016

EJEA

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“…Microarray gene expression analysis of HS5 and HS27a cells revealed prominent induction of IL-32 by TNF␣ (12). Because IL-32 appears to contribute to inflammatory and autoimmune diseases (13)(14)(15)(16) and induces TNF␣ and apoptosis (17), we hypothesized that IL-32 and TNF␣ participate in an autoamplification loop in MDS that promotes apoptosis. Therefore, the levels of TNF␣, IL-32, or both should be lower in patients in whom proliferation, rather than apoptosis, was the dominant feature.…”

mentioning

confidence: 99%

Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function

Marcondes

Mhyre

Stirewalt

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

121

107

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TNF␣ levels are elevated in the marrows of patients with myelodysplastic syndrome (MDS) and are associated with high rates of apoptosis, which contributes to hematopoietic failure. We observed that exposure of human marrow stroma cell lines HS5 and HS27a to TNF␣ increases levels of IL-32 mRNA. IL-32, in turn, induces TNF␣. Marrow stroma from patients with MDS expressed 14-to 17-fold higher levels of IL-32 mRNA than healthy controls. In contrast, cells from patients with chronic myelomonocytic leukemia (CMML) expressed only one tenth the level of IL-32 measured in healthy controls. Human KG1a leukemia cells underwent apoptosis when cocultured with HS5 stromal cells, but knockdown of IL-32 in the stromal cells by using siRNA abrogated apoptosis in the leukemia cells. IL-32 knockdown cells also showed dysregulation of VEGF and other cytokines. Furthermore, CD56 ؉ natural killer cells from patients with MDS and CMML expressed IL-32 at lower levels than controls and exhibited reduced cytotoxic activity, which was unaffected by IL-2 treatment. We propose that IL-32 is a marrow stromal marker that distinguishes patients with MDS and CMML. Furthermore, IL-32 appears to contribute to the pathophysiology of MDS and may be a therapeutic target. marrow stroma ͉ TNF␣

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“…Two recently discovered proinflammatory cytokines, IL-32 and IL-17, are associated with the pathogenesis of chronic inflammatory diseases (7,8). IL-32 (NK transcript 4), found in activated T cells, NK cells, and monocytic cells, is a potent inducer of proinflammatory mediators in diseases such as RA, atopic dermatitis, and chronic obstructive pulmonary disease (9)(10)(11).…”

mentioning

confidence: 99%

Inflammatory Cytokines IL-32 and IL-17 Have Common Signaling Intermediates despite Differential Dependence on TNF-Receptor 1

Turner-Brannen

Choi

Arsenault³

et al. 2011

The Journal of Immunology

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Cytokines IL-32 and IL-17 are emerging as critical players in the pathophysiology of immune-mediated chronic inflammatory diseases. It has been speculated that the molecular mechanisms governing IL-32– and IL-17–mediated cellular responses are differentially dependent on the TNF pathway. In this study, kinome analysis demonstrated that following stimulation with cytokine IL-32, but not IL-17, there was increased phosphorylation of a peptide target corresponding to TNF-R1. Consistent with this observation, blocking TNF-R1 resulted in a suppression of IL-32–induced downstream responses, indicating that IL-32–mediated activity may be dependent on TNF-R1. In contrast, blocking TNF-R1 did not affect IL-17–induced downstream responses. Kinome analysis also implicated p300 (transcriptional coactivator) and death-associated protein kinase-1 (DAPK-1) as signaling intermediates for both IL-32 and IL-17. Phosphorylation of p300 and DAPK-1 upon stimulation with either IL-32 or IL-17 was confirmed by immunoblots. The presence of common targets was supported by results demonstrating similar downstream responses induced in the presence of IL-32 and IL-17, such as transcriptional responses and the direct activation of NF-κB. Furthermore, knockdown of p300 and DAPK-1 altered downstream responses induced by IL-32 and IL-17, and impacted certain cellular responses induced by TNF-α and IL-1β. We hypothesize that p300 and DAPK-1 represent nodes where the inflammatory networks of IL-32 and IL-17 overlap, and that these proteins would affect both TNF-R1–dependent and –independent pathways. Therefore, p300 and DAPK-1 are viable potential therapeutic targets for chronic inflammatory diseases.

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IL-32, a novel cytokine with a possible role in disease

Cited by 154 publications

References 29 publications

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function

Inflammatory Cytokines IL-32 and IL-17 Have Common Signaling Intermediates despite Differential Dependence on TNF-Receptor 1

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