IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis

Meyer, Norbert; Zimmermann, Maya; Bürgler, Simone; Bassin, Claudio; Woehrl, Stefan; Moritz, Katharina; Rhyner, Claudio; Indermitte, Philippe; Schmid‐Grendelmeier, Peter; Akdiş, Mübeccel; Menz, Günter

doi:10.1016/j.jaci.2010.01.016

Cited by 134 publications

(156 citation statements)

References 44 publications

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“…IL-32 is known to promote apoptosis of keratinocytes in atopic dermatitis (11), which supports our results that identified an apoptosis regulator, DAPK-1, as a protein target for IL-32. Another study has shown that inflammation can lead to aberrant DNA methylation of the DAPK-1 gene in a model of IBD (40).…”

Section: Discussionsupporting

confidence: 91%

“…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). IL-32 levels are significantly elevated in RA synovial tissues and can induce joint inflammation, cartilage damage (9), and osteoclast differentiation (12).…”

mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 91%

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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“…Predominance of Th2 cells might be caused by an increased tendency to activate induced cell death of high IFN-gama producing Th1 cells as it is commonly observed in patients with atopic disorders (15). Th1 cells induce apoptosis of keratinocytes in atopic dermatitis and epithelial cells and/or smooth muscle cells in asthma in the effector phase of these allergic diseases (16)(17)(18)(19)(20). As the major consequences of the activation of mast cells, the release of histamine and other mediators occur, which leads to acute allergic reaction.…”

Section: A Ll E Rgymentioning

confidence: 99%

Histamine and Antihistamines / Histamin i antihistamini

Stojkovic¹,

Cekić²,

Ristov³

et al. 2015

Acta Facultatis Medicae Naissensis

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“…IL32 is upregulated in atopic skin lesions, in sinus tissue from CRS tissue with polyposis and correlates with disease severity in serum of patients with asthma. 3,[6][7][8] Recently a "new" Th2 type cytokine IL33 was described. It is able to act on precursor populations and dendritic cells that induce Th2 type responses and Th2 effector cell populations ultimately inducing Th2 type inflammation in the lung and the gut.…”

Section: Introductionmentioning

confidence: 99%