IL-17A potentiates TNFα-induced secretion from human endothelial cells and alters barrier functions controlling neutrophils rights of passage

Bosteen, Markus H.; Tritsaris, Katerina; Hansen, Anker Jón; Dissing, Steen

doi:10.1007/s00424-013-1354-5

Cited by 25 publications

(26 citation statements)

References 55 publications

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“…As shown in Fig 1A, Western blotting analysis confirmed the previously reported expression of IL-17 (IL-17RA) and IL-36 (IL-1Rrp2) receptor subunits in HDMECs (Fig. 1A) [11,14]. Densitometric analysis (not shown) indicated that IL-17RA and IL-1Rrp2 expression was not significantly influenced by treatment with IL-17A and IL-36γ, alone or in combination with TNF-α (Fig.1A).…”

Section: Resultssupporting

confidence: 87%

“…In the case of tumor necrosis factor (TNF)-α, IL-17A stabilizes the mRNA of TNF-activated genes leading to a signal amplification [13]. IL-17 and TNF-α synergistically stimulate cytokine expression in human melanocytes and ECs [14,15]. In human dermal microvascular ECs (HDMECs), IL-17A cooperates with TNF-α in the induction of CSF1/G-CSF and CXCL1/GRO-α [14], whereas in brain ECs IL-17A alone stimulates the release of CCL2/MCP-1 and CXCL1/GRO-α [16].…”

Section: Introductionmentioning

confidence: 99%

“…IL-17 and TNF-α synergistically stimulate cytokine expression in human melanocytes and ECs [14,15]. In human dermal microvascular ECs (HDMECs), IL-17A cooperates with TNF-α in the induction of CSF1/G-CSF and CXCL1/GRO-α [14], whereas in brain ECs IL-17A alone stimulates the release of CCL2/MCP-1 and CXCL1/GRO-α [16]. On an immortalized endothelial cell line, IL-17A was able to stimulate the release of CXCL1/GRO-α, CSF2/GM-CSF and CXCL8/IL-8 [17].…”

Section: Introductionmentioning

confidence: 99%

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Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses

Failla

Capriotti

Scarponi

et al. 2019

Preprint

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In inflammatory skin conditions, such as psoriasis, vascular enlargement is associated with endothelial cell proliferation, release of cytokines and adhesion molecule expression. Interleukin (IL)-17A is a pro-inflammatory cytokine mainly secreted by T helper-17 cells that is critically involved in psoriasis pathogenesis. IL-36α, IL-36β and IL-36γ are also inflammatory cytokines up-regulated in psoriasis and induced by various stimuli, including IL-17A. In this study, we found that human keratinocytes are the main source of IL-36, in particular of IL-36γ. This cytokine was strongly induced by IL-17A and efficiently activated human dermal microvascular endothelial cells (HDMECs), which expressed both IL-17 and IL-36 receptors, by inducing a molecular signaling, such as phosphorylation of ERK1/2 and NF-κB P65 subunit. We highlighted the intense IL-17A- and IL-36γ-dependent interplay between keratinocytes and HDMECs, likely active in the psoriatic lesions and leading to the establishment of a cytokine network responsible for the development and maintenance of the inflamed state. On HDMECs, IL-17A or IL-36γ showed a synergic activity with TNF-α, potently inducing inflammatory cytokine/chemokine release and ICAM-1 expression. We also investigated the involvement of IL-36γ and VEGF-A, substantially reduced in lesional skin of psoriatic patients pharmacologically treated with the anti-IL-17A antibody Secukinumab. Importantly, keratinocyte-derived IL-36γ represented an additional pro-angiogenic mediator of IL-17A. We observed that keratinocyte-derived VEGF-A influenced proliferation but not reduced inflammatory responses of HDMECs. On the other hand, inhibition of IL-36γ released by IL-17A-treated keratinocytes impaired ICAM-1 expression in HDMECs. Taken together, our data demonstrated that IL-17A and IL-36γ are highly involved in endothelial cells/keratinocytes crosstalk in inflammatory skin conditions.

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Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses

Failla

Capriotti

Scarponi

et al. 2019

Preprint

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“…It is therefore widely assumed that IL-17, like IL-1 and TNF, will exert its pro-inflammatory effects through activation of ECs. However, we and others have noted that effects of IL-17 on human ECs appear weak compared to the responses by several other stromal cell types such as fibroblasts, synoviocytes or vascular smooth muscle cells (10-12). The effect of IL-17 on PCs, which are related to but distinct from smooth muscle cells, has not been previously examined.…”

Section: Introductionmentioning

confidence: 69%

IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

Liu

Lauridsen

Amezquita

et al. 2016

The Journal of Immunology

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A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space.

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“…TH17 cells can release a large amount of IL‐17A to promote G‐CSF and KC secretion, and G‐CSF can mobilize neutrophils from the bone marrow to peripheral blood . KC can induce the chemotaxis of pro‐inflammatory cells in particular neutrophils to the lung, consequently increasing inflammatory monocytes and neutrophils and lymphocytes in the BALF of the mice with AE‐IPF and exacerbating the local inflammatory responses in the lung.…”

Section: Discussionmentioning

confidence: 99%

IL‐17A contributes to HSV1 infection‐induced acute lung injury in a mouse model of pulmonary fibrosis

Chen

Qiu

Zhao

et al. 2018

J Cellular Molecular Medi

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BackgroundPatients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold.AimsTo establish a mouse model of virus infection‐induced AE‐IPF and investigate the mechanism underlying the AE‐IPF.MethodsHerpes simplex virus 1 (HSV1) was inoculated intranasally to wild‐type (WT) and IL‐17A gene knockout (IL‐17A‐/‐) mice 21 days after intratracheal administration of bleomycin (BLM).Results HSV1 infection caused acute exacerbation in mice with BLM‐induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)‐related proteins in mice with BLM‐induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL‐17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE‐IPF. Compared with WT mice with BLM+HSV1, IL‐17A‐/‐ mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response.Conclusions HSV1 infection in addition to BLM‐induced IPF can successfully establish AE‐IPF in mice. IL‐17A and ERS promote lung inflammation in AE‐IPF development.

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IL-17A potentiates TNFα-induced secretion from human endothelial cells and alters barrier functions controlling neutrophils rights of passage

Cited by 25 publications

References 55 publications

Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses

Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses

IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

IL‐17A contributes to HSV1 infection‐induced acute lung injury in a mouse model of pulmonary fibrosis

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