Low concentrations of neutrophil extracellular traps induce proliferation in human keratinocytes via NF-kB activation

Tonello, Stelvio; Rizzi, Manuela; Migliario, Mario; Rocchetti, Vincenzo; Renò, Filippo

doi:10.1016/j.jdermsci.2017.05.010

Cited by 35 publications

(33 citation statements)

References 42 publications

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“…In our study, we tried to employ a cell coculture model to investigate the effects of GPP neutrophils on keratinocytes, which revealed the proinflammatory role of GPP neutrophils in this immune environment. Although some previous reports have demonstrated the proliferation of keratinocytes induced by NETs or NE (56,57), our proliferative results showed that GPP neutrophils didn't stimulate the keratinocyte proliferation in a direct or indirect coculture system. We believe that the keratinocyte proliferation when cocultured with GPP neutrophils is a result that is impacted by several factors, including high level of enzymes, granule proteins, and peroxides and the direct contact between GPP neutrophils and keratinocytes, which needs further investigation.…”

Section: Discussioncontrasting

confidence: 99%

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

et al. 2019

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Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease that can be life‐threatening. Gene mutations are found in some cases, but its immune pathogenesis is largely unknown. Here, we observed that the neutrophil:lymphocyte ratio in patients with GPP was higher than that in healthy controls and decreased after effective treatment. Neutrophils isolated from patients with GPP induced higher expressions of inflammatory genes including IL‐1β, IL‐36G, IL‐18, TNF‐α, and C‐X‐C motif chemokine ligands in keratinocytes than normal neutrophils did. Moreover, neutrophils from patients with GPP secreted more exosomes than controls, which were then rapidly internalized by keratinocytes, increasing the expression of these inflammatory molecules via activating NF‐κB and MAPK signaling pathways. The proteomic profiles in neutrophil exosomes further characterized functional proteins and identified olfactomedin 4 as the critical differentially expressed protein that mediates the autoimmune inflammatory responses of GPP. These results demonstrate that neutrophil exosomes have an immune‐regulatory effect on keratinocytes, which modulates immune cell migration and autoinflammation in GPP.—Shao, S., Fang, H., Zhang, J., Jiang, M., Xue, K., Ma, J., Zhang, J., Lei, J., Zhang, Y., Li, B., Yuan, X., Dang, E., Wang, G. Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes. FASEB J. 33, 6813–6828 (2019). http://www.fasebj.org

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Section: Discussioncontrasting

confidence: 99%

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

et al. 2019

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“…The discrepancy regarding NET-mediated regulation of fibrosis may be due to the double-edged effects of NETs 30 . Histones in NETs may damage cells 39 , while low doses of NETs increase cell proliferation and accelerate skin wound healing 40 .…”

Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps promote scar formation in post-epidural fibrosis

et al. 2020

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Low back pain following spine surgery is a major complication due to excessive epidural fibrosis, which compresses the lumbar nerve. The mechanisms of epidural fibrosis remain largely elusive. In the drainage samples from patients after spine operation, neutrophil extracellular traps (NETs) and NETs inducer high-mobility group box 1 were significantly increased. In a mouse model of laminectomy, NETs developed in the wound area post epidural operation, accompanied with macrophage infiltration. In vitro, macrophages ingested NETs and thereby increased the elastase from NETs via the receptor for advanced glycation end product. Moreover, NETs boosted the expression of fibronectin in macrophages, which was dependent on elastase and could be partially blocked by DNase. NF-κB p65 and Smad pathways contributed to the increased expression fibronectin in NETs-treated macrophages. In the mouse spine operation model, post-epidural fibrosis was significantly mitigated with the administration of DNase I, which degraded DNA and cleaved NETs. Our study shed light on the roles and mechanisms of NETs in the scar formation post spine operation.

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“…Part of the DMSO anti-proliferative effect could be attributed to its action over the production of IL-2 cytokine. Santos et al (2015) [ 19 ] observed that DMSO up to 0.5% v/v did not modify IL-2 production in PBMC cultures after stimulation with PHA for 36 h. However, its effect observed on cell proliferation cannot be attributed only to the reduction of IL-2 cytokine production, since other many mediators, such as Ca 2+ and NF-κB, are also involved in cell proliferation stimulation [ 20 , 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Dimethyl Sulfoxide (DMSO) Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes

et al. 2017

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Dimethylsulfoxide (DMSO) is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs of therapeutic applications and studies indicated that 10% v/v concentration did not modify culture viability when used to treat human peripheral blood mononuclear cells (PBMC). However, some DMSO concentrations could influence lymphocyte activation and present anti-inflammatory effects. Therefore, the objective of this study was to evaluate the effect of DMSO on lymphocyte activation parameters. Cell viability analysis, proliferation, and cytokine production were performed on PBMC from six healthy subjects by flow cytometry. The results indicated that 2.5% v/v DMSO concentrations did not modify lymphocytes viability. DMSO at 1% and 2% v/v concentrations reduced the relative proliferation index of lymphocytes and at 5% and 10% v/v concentrations reduced the percentage of total lymphocytes, cluster of differentiation 4+ (CD4+) T lymphocytes and CD8+ T lymphocytes interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) producers. Thus, it was concluded that DMSO has an in vitro anti-inflammatory effect by reducing lymphocyte activation demonstrated with proliferation reduction and the decrease of cytokine production.

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Low concentrations of neutrophil extracellular traps induce proliferation in human keratinocytes via NF-kB activation

Cited by 35 publications

References 42 publications

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

Neutrophil extracellular traps promote scar formation in post-epidural fibrosis

Dimethyl Sulfoxide (DMSO) Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes

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